2,014
Views
21
CrossRef citations to date
0
Altmetric
Review

The role of splicing factors in deregulation of alternative splicing during oncogenesis and tumor progression

, &
Article: e970955 | Received 23 Jul 2014, Accepted 15 Sep 2014, Published online: 24 Feb 2015

References

  • Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 2008; 40:1413-5; PMID:18978789; http://dx.doi.org/10.1038/ng.259
  • Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore SF, Schroth GP, Burge CB. Alternative isoform regulation in human tissue transcriptomes. Nature 2008; 456:470-6; PMID:18978772; http://dx.doi.org/10.1038/nature07509
  • Chen M, Manley JL. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat Rev Mol Cell Biol 2009; 10:741-54; PMID:19773805
  • Wahl MC, Will CL, Luhrmann R. The spliceosome: design principles of a dynamic RNP machine. Cell 2009; 136, 701-18; PMID:19239890; http://dx.doi.org/10.1016/j.cell.2009.02.009
  • Xu Q, Lee C. Discovery of novel splice forms and functional analysis of cancer-specific alternative splicing in human expressed sequences. Nucleic Acids Res 2003; 31:5635-43; PMID:14500827; http://dx.doi.org/10.1093/nar/gkg786
  • Hui L, Zhang X, Wu X, Lin Z, Wang Q, Li Y, Hu G. Identification of alternatively spliced mRNA variants related to cancers by genome-wide ESTs alignment. Oncogene 2004; 23:3013-23; PMID:15048092; http://dx.doi.org/10.1038/sj.onc.1207362
  • Venables JP, Klinck R, Koh C, Gervais-Bird J, Bramard A, Inkel L, Durand M, Couture S, Froehlich U, Lapointe E, et al. Cancer-associated regulation of alternative splicing. Nat Struct Mol Biol 2009; 16:670-6; PMID:19448617; http://dx.doi.org/10.1038/nsmb.1608
  • Thorsen K, Sørensen KD, Brems-Eskildsen AS, Modin C, Gaustadnes M, Hein AM, Kruhøffer M, Laurberg S, Borre M, Wang K, et al. Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis. Mol Cell Proteomics 2008; 7:1214-24; PMID:18353764; http://dx.doi.org/10.1074/mcp.M700590-MCP200
  • Guo X, Chen QR, Song YK, Wei JS, Khan J. Exon array analysis reveals neuroblastoma tumors have distinct alternative splicing patterns according to stage and MYCN amplification status. BMC Med Genomics 2011; 4:35; PMID:21501490; http://dx.doi.org/10.1186/1755-8794-4-35
  • Venables JP. Unbalanced alternative splicing and its significance in cancer. Bioessays 2006; 28:378-86; PMID:16547952; http://dx.doi.org/10.1002/bies.20390
  • Cohen-Eliav M, Golan-Gerstl R, Siegfried Z, Andersen CL, Thorsen K, Ørntoft TF, Mu D, Karni R. The splicing factor SRSF6 is amplified and is an oncoprotein in lung and colon cancers. J Pathol 2013; 229:630-9; PMID:23132731; http://dx.doi.org/10.1002/path.4129
  • Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR. The gene encoding the splicing factor SF2ASF is a proto-oncogene. Nat Struct Mol Biol 2007; 14:185-93; PMID:17310252; http://dx.doi.org/10.1038/nsmb1209
  • Golan-Gerstl R, Cohen M, Shilo A, Suh SS, Bakàcs A, Coppola L, Karni R. Splicing factor hnRNP A2B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma. Cancer Res 2011; 71:4464-72; PMID:21586613; http://dx.doi.org/10.1158/0008-5472.CAN-10-4410
  • Lefave CV, Squatrito M, Vorlova S, Rocco GL, Brennan CW, Holland EC, Pan YX, Cartegni L. Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas. EMBO J 2011; 30:4084-97; PMID:21915099; http://dx.doi.org/10.1038/emboj.2011.259
  • Jia R, Li C, McCoy JP, Deng CX, Zheng ZM. SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance. Int J Biol Sci 2010; 6:806-26; PMID:21179588; http://dx.doi.org/10.7150/ijbs.6.806
  • Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011; 478:64-9; PMID:21909114; http://dx.doi.org/10.1038/nature10496
  • Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013; 368:2059-74; PMID:23634996; http://dx.doi.org/10.1056/NEJMoa1301689
  • Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012; 150:1107-20; PMID:22980975; http://dx.doi.org/10.1016/j.cell.2012.08.029
  • Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet 2013; 45:133-5; PMID:23313955; http://dx.doi.org/10.1038/ng.2523
  • Comprehensive molecular portraits of human breast tumours. Nature 2012; 490:61-70; PMID:23000897; http://dx.doi.org/10.1038/nature11412
  • Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D, Pellagatti A, Wainscoat JS, Hellstrom-Lindberg E, Gambacorti-Passerini C, et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med 2011; 365:1384-95; PMID:21995386; http://dx.doi.org/10.1056/NEJMoa1103283
  • Makishima H, Visconte V, Sakaguchi H, Jankowska AM, Abu Kar S, Jerez A, Przychodzen B, Bupathi M, Guinta K, Afable MG, et al. Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood 2012; 119:3203-10; PMID:22323480; http://dx.doi.org/10.1182/blood-2011-12-399774
  • de la Mata M, Alonso CR, Kadener S, Fededa JP, Blaustein M, Pelisch F, Cramer P, Bentley D, Kornblihtt AR. A slow RNA polymerase II affects alternative splicing in vivo. Mol Cell 2003; 12:525-32; PMID:14536091; http://dx.doi.org/10.1016/j.molcel.2003.08.001
  • Munoz MJ, Pérez Santangelo MS, Paronetto MP, de la Mata M, Pelisch F, Boireau S, Glover-Cutter K, Ben-Dov C, Blaustein M, Lozano JJ, et al. DNA damage regulates alternative splicing through inhibition of RNA polymerase II elongation. Cell 2009; 137:708-20; PMID:19450518; http://dx.doi.org/10.1016/j.cell.2009.03.010
  • Dujardin G, Lafaille C, de la Mata M, Marasco LE, Muñoz MJ, Le Jossic-Corcos C, Corcos L, Kornblihtt AR. How slow RNA polymerase II elongation favors alternative exon skipping. Mol Cell 2014; 54:683-90; PMID:24793692; http://dx.doi.org/10.1016/j.molcel.2014.03.044
  • Luco RF, Pan Q, Tominaga K, Blencowe BJ, Pereira-Smith OM, Misteli T. Regulation of alternative splicing by histone modifications. Science 2010; 327:996-1000; PMID:20133523; http://dx.doi.org/10.1126/science.1184208
  • Luco RF, Misteli T. More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation. Curr Opin Genet Dev 2011; 21:366-72; PMID:21497503; http://dx.doi.org/10.1016/j.gde.2011.03.004
  • Weir BA, Woo MS, Getz G, Perner S, Ding L, Beroukhim R, Lin WM, Province MA, Kraja A, Johnson LA, et al. Characterizing the cancer genome in lung adenocarcinoma. Nature 2007; 450:893-8; PMID:17982442; http://dx.doi.org/10.1038/nature06358
  • Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008; 455:1061-8; PMID:18772890; http://dx.doi.org/10.1038/nature07385
  • Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, Sougnez C, Greulich H, Muzny DM, Morgan MB, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 2008; 455:1069-75; PMID:18948947; http://dx.doi.org/10.1038/nature07423
  • Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, et al. The consensus coding sequences of human breast and colorectal cancers. Science 2006; 314:268-74; PMID:16959974; http://dx.doi.org/10.1126/science.1133427
  • Graubert TA, Shen D, Ding L, Okeyo-Owuor T, Lunn CL, Shao J, Krysiak K, Harris CC, Koboldt DC, Larson DE, et al. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet 2012; 44:53-7; PMID:22158538; http://dx.doi.org/10.1038/ng.1031
  • Visconte V, Makishima H, Jankowska A, Szpurka H, Traina F, Jerez A, O'Keefe C, Rogers HJ, Sekeres MA, Maciejewski JP, et al. SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts. Leukemia 2012; 26:542-5; PMID:21886174; http://dx.doi.org/10.1038/leu.2011.232
  • Lasho TL, Jimma T, Finke CM, Patnaik M, Hanson CA, Ketterling RP, Pardanani A, Tefferi A. SRSF2 mutations in primary myelofibrosis: significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival. Blood 2012; 120:4168-71; PMID:22968464; http://dx.doi.org/10.1182/blood-2012-05-429696
  • Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, Werner L, Sivachenko A, DeLuca DS, Zhang L, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011; 365:2497-506; PMID:22150006; http://dx.doi.org/10.1056/NEJMoa1109016
  • Hirabayashi S, Flotho C, Moetter J, Heuser M, Hasle H, Gruhn B, Klingebiel T, Thol F, Schlegelberger B, Baumann I, et al. Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML. Blood 2012; 119:e96-9; PMID:22238327; http://dx.doi.org/10.1182/blood-2011-12-395087
  • Wan Y, Wu CJ. SF3B1 mutations in chronic lymphocytic leukemia. Blood 2013; 121:4627-34; PMID:23568491; http://dx.doi.org/10.1182/blood-2013-02-427641
  • Scott LM, Rebel VI. Acquired mutations that affect pre-mRNA splicing in hematologic malignancies and solid tumors. J Natl Cancer Inst 2013; 105:1540-9; PMID:24052622; http://dx.doi.org/10.1093/jnci/djt257
  • Yoshida K, Ogawa S. Splicing factor mutations and cancer. WIREs RNA, 2014, 5:445-459.
  • Cazzola M, Rossi M, Malcovati L. Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms. Blood 2013; 121:260-9; PMID:23160465; http://dx.doi.org/10.1182/blood-2012-09-399725
  • Anczukow O, Anczuków O, Rosenberg AZ, Akerman M, Das S, Zhan L, Karni R, Muthuswamy SK, Krainer AR. The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nat Struct Mol Biol 2012; 19:220-8; PMID:22245967; http://dx.doi.org/10.1038/nsmb.2207
  • Jensen MA, Wilkinson JE, Krainer AR. Splicing factor SRSF6 promotes hyperplasia of sensitized skin. Nat Struct Mol Biol 2014; 21:189-97; PMID:24440982; http://dx.doi.org/10.1038/nsmb.2756
  • Hu J, Ho AL, Yuan L, Hu B, Hua S, Hwang SS, Zhang J, Hu T, Zheng H, Gan B, et al. From the Cover: Neutralization of terminal differentiation in gliomagenesis. Proc Natl Acad Sci U S A 2013; 110:14520-7; PMID:23918370; http://dx.doi.org/10.1073/pnas.1308610110
  • Naro C, Sette C. Phosphorylation-mediated regulation of alternative splicing in cancer. Int J Cell Biol 2013; 2013:151839; PMID:24069033; http://dx.doi.org/10.1155/2013/151839
  • Stamm S. Regulation of alternative splicing by reversible protein phosphorylation. J Biol Chem 2008; 283:1223-7; PMID:18024427; http://dx.doi.org/10.1074/jbc.R700034200
  • Shin C, Manley JL. The SR protein SRp38 represses splicing in M phase cells. Cell 2002; 111:407-17; PMID:12419250; http://dx.doi.org/10.1016/S0092-8674(02)01038-3
  • Feng Y, Chen M, Manley JL. Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator. Nat Struct Mol Biol 2008; 15:1040-8; PMID:18794844; http://dx.doi.org/10.1038/nsmb.1485
  • van der Houven van Oordt W, Diaz-Meco MT, Lozano J, Krainer AR, Moscat J, Cáceres JF. The MKK(36)-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation. J Cell Biol 2000; 149:307-16; PMID:10769024; http://dx.doi.org/10.1083/jcb.149.2.307
  • Zhou Z, Qiu J, Liu W, Zhou Y, Plocinik RM, Li H, Hu Q, Ghosh G, Adams JA, Rosenfeld MG, et al. The Akt-SRPK-SR axis constitutes a major pathway in transducing EGF signaling to regulate alternative splicing in the nucleus. Mol Cell 2012; 47:422-33; PMID:22727668; http://dx.doi.org/10.1016/j.molcel.2012.05.014
  • Bielli P, Busa R, Paronetto MP, Sette C. The RNA-binding protein Sam68 is a multifunctional player in human cancer. Endocr Relat Cancer 2011; 18:R91-R102; PMID:21565971; http://dx.doi.org/10.1530/ERC-11-0041
  • Elliott DJ, Rajan P. The role of the RNA-binding protein Sam68 in mammary tumourigenesis. J Pathol 2010; 222:223-6; PMID:20730808; http://dx.doi.org/10.1002/path.2753
  • Bechara EG, Sebestyen E, Bernardis I, Eyras E, Valcarcel J. RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation. Mol Cell 2013; 52:720-33; PMID:24332178; http://dx.doi.org/10.1016/j.molcel.2013.11.010
  • Sutherland LC, Wang K, Robinson AG. RBM5 as a putative tumor suppressor gene for lung cancer. J Thorac Oncol 2010; 5:294-8; PMID:20186023; http://dx.doi.org/10.1097/JTO.0b013e3181c6e330
  • Lin JC, Lin CY, Tarn WY, Li FY. Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events. RNA 2014; 20:1621-31; PMID:25140042; http://dx.doi.org/10.1261/rna.045583.114
  • Lopez de Silanes I, Fan J, Yang X, Zonderman AB, Potapova O, Pizer ES, Gorospe M. Role of the RNA-binding protein HuR in colon carcinogenesis. Oncogene 2003; 22:7146-54; PMID:14562043; http://dx.doi.org/10.1038/sj.onc.1206862
  • Denkert C, Weichert W, Pest S, Koch I, Licht D, Köbel M, Reles A, Sehouli J, Dietel M, Hauptmann S. Overexpression of the embryonic-lethal abnormal vision-like protein HuR in ovarian carcinoma is a prognostic factor and is associated with increased cyclooxygenase 2 expression. Cancer Res 2004; 64:189-95; PMID:14729623; http://dx.doi.org/10.1158/0008-5472.CAN-03-1987
  • Heinonen M, Bono P, Narko K, Chang SH, Lundin J, Joensuu H, Furneaux H, Hla T, Haglund C, Ristimäki A. Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma. Cancer Res 2005; 65:2157-61; PMID:15781626; http://dx.doi.org/10.1158/0008-5472.CAN-04-3765
  • Long JC, Caceres JF. The SR protein family of splicing factors: master regulators of gene expression. Biochem J 2009; 417:15-27; PMID:19061484; http://dx.doi.org/10.1042/BJ20081501
  • Zhang Z, Krainer AR. Involvement of SR proteins in mRNA surveillance. Mol Cell 2004; 16:597-607; PMID:15546619; http://dx.doi.org/10.1016/j.molcel.2004.10.031
  • Twyffels L, Gueydan C, Kruys V. Shuttling SR proteins: more than splicing factors. FEBS J 2011; 278:3246-55; PMID:21794093; http://dx.doi.org/10.1111/j.1742-4658.2011.08274.x
  • Sanford JR, Gray NK, Beckmann K, Caceres JF. A novel role for shuttling SR proteins in mRNA translation. Genes Dev 2004; 18:755-68; PMID:15082528; http://dx.doi.org/10.1101/gad.286404
  • Li X, Manley JL. Inactivation of the SR protein splicing factor ASFSF2 results in genomic instability. Cell 2005; 122:365-78; PMID:16096057; http://dx.doi.org/10.1016/j.cell.2005.06.008
  • Li X, Wang J, Manley JL. Loss of splicing factor ASFSF2 induces G2 cell cycle arrest and apoptosis, but inhibits internucleosomal DNA fragmentation. Genes Dev 2005; 19:2705-14; PMID:16260492; http://dx.doi.org/10.1101/gad.1359305
  • Wu H, Sun S, Tu K, Gao Y, Xie B, Krainer AR, Zhu J. A splicing-independent function of SF2ASF in microRNA processing. Mol Cell 2010; 38:67-77; PMID:20385090; http://dx.doi.org/10.1016/j.molcel.2010.02.021
  • Das S, Krainer AR. Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer. Mol Cancer Res 2014; 12:1195-204; PMID:24807918; http://dx.doi.org/10.1158/1541-7786.MCR-14-0131
  • Gout S, Brambilla E, Boudria A, Drissi R, Lantuejoul S, Gazzeri S, Eymin B. Abnormal expression of the pre-mRNA splicing regulators SRSF1, SRSF2, SRPK1 and SRPK2 in non small cell lung carcinoma. PLoS One 2012; 7:e46539; PMID:23071587; http://dx.doi.org/10.1371/journal.pone.0046539
  • Karni R, Hippo Y, Lowe SW, Krainer AR. The splicing-factor oncoprotein SF2ASF activates mTORC1. Proc Natl Acad Sci USA 2008; 105:15323-7; PMID:18832178; http://dx.doi.org/10.1073/pnas.0801376105
  • Michlewski G, Sanford JR, Caceres JF. The splicing factor SF2ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1. Mol Cell 2008; 30:179-89; PMID:18439897; http://dx.doi.org/10.1016/j.molcel.2008.03.013
  • Shimoni-Sebag A, Lebenthal-Loinger I, Zender L, Karni R. RRM1 domain of the splicing oncoprotein SRSF1 is required for MEK1-MAPK-ERK activation and cellular transformation. Carcinogenesis 2013; 34:2498-504; PMID:23843040; http://dx.doi.org/10.1093/carcin/bgt247
  • Olshavsky NA, Comstock CE, Schiewer MJ, Augello MA, Hyslop T, Sette C, Zhang J, Parysek LM, Knudsen KE. Identification of ASFSF2 as a critical, allele-specific effector of the cyclin D1b oncogene. Cancer Res 2010; 70:3975-84; PMID:20460515; http://dx.doi.org/10.1158/0008-5472.CAN-09-3468
  • Shultz JC, Goehe RW, Murudkar CS, Wijesinghe DS, Mayton EK, Massiello A, Hawkins AJ, Mukerjee P, Pinkerman RL, Park MA, et al. SRSF1 regulates the alternative splicing of caspase 9 via a novel intronic splicing enhancer affecting the chemotherapeutic sensitivity of non-small cell lung cancer cells. Mol Cancer Res 2011; 9:889-900; PMID:21622622; http://dx.doi.org/10.1158/1541-7786.MCR-11-0061
  • Maimon A, Mogilevsky M, Shilo A, Golan-Gerstl R, Obiedat A, Ben-Hur V, Lebenthal-Loinger I, Stein I, Reich R, Beenstock J, et al. Mnk2 Alternative Splicing Modulates the p38-MAPK Pathway and Impacts Ras-Induced Transformation. Cell Rep 2014; 7:501-13; PMID:24726367; http://dx.doi.org/10.1016/j.celrep.2014.03.041
  • Adesso L, Calabretta S, Barbagallo F, Capurso G, Pilozzi E, Geremia R, Delle Fave G, Sette C. Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2eIF4E pathway. Oncogene 2013; 32:2848-57; PMID:22797067; http://dx.doi.org/10.1038/onc.2012.306
  • Ben-Hur V, Denichenko P, Siegfried Z, Maimon A, Krainer A, Davidson B, Karni R. S6K1 alternative splicing modulates its oncogenic activity and regulates mTORC1. Cell Rep 2013; 3:103-15; PMID:23273915; http://dx.doi.org/10.1016/j.celrep.2012.11.020
  • Ghigna C, Giordano S, Shen H, Benvenuto F, Castiglioni F, Comoglio PM, Green MR, Riva S, Biamonti G. Cell motility is controlled by SF2ASF through alternative splicing of the Ron protooncogene. Mol Cell 2005; 20:881-90; PMID:16364913; http://dx.doi.org/10.1016/j.molcel.2005.10.026
  • Edmond V, Merdzhanova G, Gout S, Brambilla E, Gazzeri S, Eymin B. A new function of the splicing factor SRSF2 in the control of E2F1-mediated cell cycle progression in neuroendocrine lung tumors. Cell Cycle 2013; 12:1267-78; PMID:23518498; http://dx.doi.org/10.4161/cc.24363
  • Shi J, Hu Z, Pabon K, Scotto KW. Caffeine regulates alternative splicing in a subset of cancer-associated genes: a role for SC35. Mol Cell Biol 2008; 28:883-95; PMID:18025108; http://dx.doi.org/10.1128/MCB.01345-07
  • Merdzhanova G, Gout S, Keramidas M, Edmond V, Coll JL, Brambilla C, Brambilla E, Gazzeri S, Eymin B. The transcription factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth factor-A to inhibit neovascularization in vivo. Oncogene 2010; 29:5392-403; PMID:20639906; http://dx.doi.org/10.1038/onc.2010.281
  • Merdzhanova G, Edmond V, De Seranno S, Van den Broeck A, Corcos L, Brambilla C, Brambilla E, Gazzeri S, Eymin B. E2F1 controls alternative splicing pattern of genes involved in apoptosis through upregulation of the splicing factor SC35. Cell Death Differ 2008; 15:1815-23; PMID:18806759; http://dx.doi.org/10.1038/cdd.2008.135
  • Edmond V, Moysan E, Khochbin S, Matthias P, Brambilla C, Brambilla E, Gazzeri S, Eymin B. Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin. EMBO J 2011; 30:510-23; PMID:21157427; http://dx.doi.org/10.1038/emboj.2010.333
  • Corbo C, Orru S, Salvatore F. SRp20: an overview of its role in human diseases. Biochem Biophys Res Commun 2013; 436:1-5; PMID:23685143; http://dx.doi.org/10.1016/j.bbrc.2013.05.027
  • He X, Ee PL, Coon JS, Beck WT. Alternative splicing of the multidrug resistance protein 1ATP binding cassette transporter subfamily gene in ovarian cancer creates functional splice variants and is associated with increased expression of the splicing factors PTB and SRp20. Clin Cancer Res 2004; 10:4652-60; PMID:15269137; http://dx.doi.org/10.1158/1078-0432.CCR-03-0439
  • He X, Arslan AD, Pool MD, Ho TT, Darcy KM, Coon JS, Beck WT. Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer. Oncogene 2011; 30:356-65; PMID:20856201; http://dx.doi.org/10.1038/onc.2010.426
  • Chen W, Itoyama T, Chaganti RS. Splicing factor SRP20 is a novel partner of BCL6 in a t(3;6)(q27;p21) translocation in transformed follicular lymphoma. Genes Chromosomes Cancer 2001; 32:281-4; PMID:11579468; http://dx.doi.org/10.1002/gcc.1191
  • Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 1992; 258:1650-4; PMID:1360704; http://dx.doi.org/10.1126/science.1360704
  • Fu Y, Huang B, Shi Z, Han J, Wang Y, Huangfu J, Wu W. SRSF1 and SRSF9 RNA binding proteins promote Wnt signalling-mediated tumorigenesis by enhancing beta-catenin biosynthesis. EMBO Mol Med 2013; 5:737-50; PMID:23592547; http://dx.doi.org/10.1002/emmm.201202218
  • Dreyfuss G, Matunis MJ, Pinol-Roma S, Burd CG. hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem 1993; 62:289-321; PMID:8352591; http://dx.doi.org/10.1146/annurev.bi.62.070193.001445
  • Carpenter B, MacKay C, Alnabulsi A, MacKay M, Telfer C, Melvin WT, Murray GI. The roles of heterogeneous nuclear ribonucleoproteins in tumour development and progression. Biochim Biophys Acta 2006; 1765:85-100; PMID:16378690
  • Ushigome M, Ubagai T, Fukuda H, Tsuchiya N, Sugimura T, Takatsuka J, Nakagama H. Up-regulation of hnRNP A1 gene in sporadic human colorectal cancers. Int J Oncol 2005; 26:635-40; PMID:15703818
  • Boukakis G, Patrinou-Georgoula M, Lekarakou M, Valavanis C, Guialis A. Deregulated expression of hnRNP AB proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumournon-tumour tissues. BMC Cancer 2010; 10:434; PMID:20716340; http://dx.doi.org/10.1186/1471-2407-10-434
  • Zhou ZJ, Dai Z, Zhou SL, Fu XT, Zhao YM, Shi YH, Zhou J, Fan J. Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma. Int J Cancer 2013; 132:1080-9; PMID:22821376; http://dx.doi.org/10.1002/ijc.27742
  • Biamonti G, Bassi MT, Cartegni L, Mechta F, Buvoli M, Cobianchi F, Riva S. Human hnRNP protein A1 gene expression. Structural and functional characterization of the promoter. J Mol Biol 1993; 230:77-89; PMID:8383772; http://dx.doi.org/10.1006/jmbi.1993.1127
  • Zerbe LK, Pino I, Pio R, Cosper PF, Dwyer-Nield LD, Meyer AM, Port JD, Montuenga LM, Malkinson AM. Relative amounts of antagonistic splicing factors, hnRNP A1 and ASFSF2, change during neoplastic lung growth: implications for pre-mRNA processing. Mol Carcinog 2004; 41:187-96; PMID:15390079; http://dx.doi.org/10.1002/mc.20053
  • Clower CV, Chatterjee D, Wang Z, Cantley LC, Vander Heiden MG, Krainer AR. The alternative splicing repressors hnRNP A1A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci USA 2010; 107:1894-9; PMID:20133837; http://dx.doi.org/10.1073/pnas.0914845107
  • David CJ, Manley JL. Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev 2010; 24:2343-64; PMID:21041405; http://dx.doi.org/10.1101/gad.1973010
  • Shilo A, Ben Hur V, Denichenko P, Stein I, Pikarsky E, Rauch J, Kolch W, Zender L, Karni R. Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development. RNA 2014; 20:505-15; PMID:24572810; http://dx.doi.org/10.1261/rna.042259.113
  • Bonomi S, di Matteo A, Buratti E, Cabianca DS, Baralle FE, Ghigna C, Biamonti G. HnRNP A1 controls a splicing regulatory circuit promoting mesenchymal-to-epithelial transition. Nucleic Acids Res 2013; 41:8665-79; PMID:23863836; http://dx.doi.org/10.1093/nar/gkt579
  • Zhou J, Allred DC, Avis I, Martínez A, Vos MD, Smith L, Treston AM, Mulshine JL. Differential expression of the early lung cancer detection marker, heterogeneous nuclear ribonucleoprotein-A2B1 (hnRNP-A2B1) in normal breast and neoplastic breast cancer. Breast Cancer Res Treat 2001; 66:217-24; PMID:11510693; http://dx.doi.org/10.1023/A:1010631915831
  • Lee CH, Lum JH, Cheung BP, Wong MS, Butt YK, Tam MF, Chan WY, Chow C, Hui PK, Kwok FS, et al. Identification of the heterogeneous nuclear ribonucleoprotein A2B1 as the antigen for the gastrointestinal cancer specific monoclonal antibody MG7. Proteomics 2005; 5:1160-6; PMID:15759317; http://dx.doi.org/10.1002/pmic.200401159
  • Fielding P, Turnbull L, Prime W, Walshaw M, Field JK. Heterogeneous nuclear ribonucleoprotein A2B1 up-regulation in bronchial lavage specimens: a clinical marker of early lung cancer detection. Clin Cancer Res 1999; 5:4048-52; PMID:10632338
  • Zhou J, Nong L, Wloch M, Cantor A, Mulshine JL, Tockman MS. Expression of early lung cancer detection marker: hnRNP-A2B1 and its relation to microsatellite alteration in non-small cell lung cancer. Lung Cancer 2001; 34:341-50; PMID:11714531; http://dx.doi.org/10.1016/S0169-5002(01)00254-9
  • Yan-Sanders Y, Hammons GJ, Lyn-Cook BD. Increased expression of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNP) in pancreatic tissue from smokers and pancreatic tumor cells. Cancer Lett 2002; 183:215-20; PMID:12065097; http://dx.doi.org/10.1016/S0304-3835(02)00168-4
  • Kozu T, Henrich B, Schafer KP. Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2B1. Genomics 1995; 25:365-71; PMID:7789969; http://dx.doi.org/10.1016/0888-7543(95)80035-K
  • Matsuyama S, Goto Y, Sueoka N, Ohkura Y, Tanaka Y, Nakachi K, Sueoka E. Heterogeneous nuclear ribonucleoprotein B1 expressed in esophageal squamous cell carcinomas as a new biomarker for diagnosis. Jpn J Cancer Res 2000; 91:658-63; PMID:10874220; http://dx.doi.org/10.1111/j.1349-7006.2000.tb00996.x
  • Wu S, Sato M, Endo C, Sakurada A, Dong B, Aikawa H, Chen Y, Okada Y, Matsumura Y, Sueoka E, et al. hnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung. Lung Cancer 2003; 41:179-86; PMID:12871781; http://dx.doi.org/10.1016/S0169-5002(03)00226-5
  • Snead DR, Perunovic B, Cullen N, Needham M, Dhillon DP, Satoh H, Kamma H. hnRNP B1 expression in benign and malignant lung disease. J Pathol 2003; 200:88-94; PMID:12692846; http://dx.doi.org/10.1002/path.1292
  • Sueoka E, Sueoka N, Goto Y, Matsuyama S, Nishimura H, Sato M, Fujimura S, Chiba H, Fujiki H. Heterogeneous nuclear ribonucleoprotein B1 as early cancer biomarker for occult cancer of human lungs and bronchial dysplasia. Cancer Res 2001; 61:1896-902; PMID:11280744
  • Tominaga M, Sueoka N, Irie K, Iwanaga K, Tokunaga O, Hayashi S, Nakachi K, Sueoka E. Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin D1, and Ki-67. Lung Cancer 2003; 40:45-53; PMID:12660006; http://dx.doi.org/10.1016/S0169-5002(02)00529-9
  • Patry C, Bouchard L, Labrecque P, Gendron D, Lemieux B, Toutant J, Lapointe E, Wellinger R, Chabot B. Small interfering RNA-mediated reduction in heterogeneous nuclear ribonucleoparticule A1A2 proteins induces apoptosis in human cancer cells but not in normal mortal cell lines. Cancer Res 2003; 63:7679-88; PMID:14633690
  • He Y, Brown MA, Rothnagel JA, Saunders NA, Smith R. Roles of heterogeneous nuclear ribonucleoproteins A and B in cell proliferation. J Cell Sci 2005; 118:3173-83; PMID:16014382; http://dx.doi.org/10.1242/jcs.02448
  • David CJ, Chen M, Assanah M, Canoll P, Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 2010; 463:364-8; PMID:20010808; http://dx.doi.org/10.1038/nature08697
  • Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008; 452:230-3; PMID:18337823; http://dx.doi.org/10.1038/nature06734
  • Kim JH, Paek KY, Choi K, Kim TD, Hahm B, Kim KT, Jang SK. Heterogeneous nuclear ribonucleoprotein C modulates translation of c-myc mRNA in a cell cycle phase-dependent manner. Mol Cell Biol 2003; 23:708-20; PMID:12509468; http://dx.doi.org/10.1128/MCB.23.2.708-720.2003
  • Rauch J, O'Neill E, Mack B, Matthias C, Munz M, Kolch W, Gires O. Heterogeneous nuclear ribonucleoprotein H blocks MST2-mediated apoptosis in cancer cells by regulating A-Raf transcription. Cancer Res 2010; 70:1679-88; PMID:20145135; http://dx.doi.org/10.1158/0008-5472.CAN-09-2740
  • Rauch J, Moran-Jones K, Albrecht V, Schwarzl T, Hunter K, Gires O, Kolch W. c-Myc regulates RNA splicing of the A-Raf kinase and its activation of the ERK pathway. Cancer Res 2011; 71:4664-74; PMID:21512137; http://dx.doi.org/10.1158/0008-5472.CAN-10-4447
  • Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, Shiue L, Ares M Jr, Black DL. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev 2007; 21:1636-52; PMID:17606642; http://dx.doi.org/10.1101/gad.1558107
  • Keppetipola N, Sharma S, Li Q, Black DL. Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2. Crit Rev Biochem Mol Biol 2012; 47:360-78; PMID:22655688; http://dx.doi.org/10.3109/10409238.2012.691456
  • He X, Pool M, Darcy KM, Lim SB, Auersperg N, Coon JS, Beck WT. Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro. Oncogene 2007; 26:4961-8; PMID:17310993; http://dx.doi.org/10.1038/sj.onc.1210307
  • Jin W, McCutcheon IE, Fuller GN, Huang ES, Cote GJ. Fibroblast growth factor receptor-1 alpha-exon exclusion and polypyrimidine tract-binding protein in glioblastoma multiforme tumors. Cancer Res 2000; 60:1221-4; PMID:10728679
  • He X, Arslan AD2, Ho TT2, Yuan C3, Stampfer MR4, Beck WT5. Involvement of polypyrimidine tract-binding protein (PTBP1) in maintaining breast cancer cell growth and malignant properties. Oncogenesis 2014; 3:e84; PMID:24418892; http://dx.doi.org/10.1038/oncsis.2013.47
  • Chen S, Zhang J, Duan L, Zhang Y, Li C, Liu D, Ouyang C, Lu F, Liu X. Identification of HnRNP M as a novel biomarker for colorectal carcinoma by quantitative proteomics. Am J Physiol Gastrointest Liver Physiol 2014; 306:G394-403; PMID:24381081; http://dx.doi.org/10.1152/ajpgi.00328.2013
  • Xu Y, Gao XD, Lee JH, Huang H, Tan H, Ahn J, Reinke LM, Peter ME, Feng Y, Gius D, et al. Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing. Genes Dev 2014; 28:1191-203; PMID:24840202; http://dx.doi.org/10.1101/gad.241968.114
  • Warzecha CC, Sato TK, Nabet B, Hogenesch JB, Carstens RP. ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing. Mol Cell 2009; 33:591-601; PMID:19285943; http://dx.doi.org/10.1016/j.molcel.2009.01.025
  • Pino I, Pío R, Toledo G, Zabalegui N, Vicent S, Rey N, Lozano MD, Torre W, García-Foncillas J, Montuenga LM. Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer. Lung Cancer 2003; 41:131-43; PMID:12871776; http://dx.doi.org/10.1016/S0169-5002(03)00193-4
  • Ostrowski J, Bomsztyk K. Nuclear shift of hnRNP K protein in neoplasms and other states of enhanced cell proliferation. Br J Cancer 2003; 89:1493-501; PMID:14562022; http://dx.doi.org/10.1038/sj.bjc.6601250
  • Matta A, Tripathi SC, DeSouza LV, Grigull J, Kaur J, Chauhan SS, Srivastava A, Thakar A, Shukla NK, Duggal R, et al. Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma. Int J Cancer 2009; 125:1398-406; PMID:19548310; http://dx.doi.org/10.1002/ijc.24517
  • Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 2008; 14:818-29; PMID:18539112; http://dx.doi.org/10.1016/j.devcel.2008.05.009
  • Mani SA, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N, Kutok JL, Hartwell K, Richardson AL, Weinberg RA. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci U S A 2007; 104:10069-74; PMID:17537911; http://dx.doi.org/10.1073/pnas.0703900104
  • Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927-39; PMID:15210113; http://dx.doi.org/10.1016/j.cell.2004.06.006
  • Biamonti G, Bonomi S, Gallo S, Ghigna C. Making alternative splicing decisions during epithelial-to-mesenchymal transition (EMT). Cell Mol 2012; Life Sci 69:2515-26; PMID:22349259; http://dx.doi.org/10.1007/s00018-012-0931-7
  • Pino MS, Balsamo M, Di Modugno F, Mottolese M, Alessio M, Melucci E, Milella M, McConkey DJ, Philippar U, Gertler FB, et al. Human Mena+11a isoform serves as a marker of epithelial phenotype and sensitivity to epidermal growth factor receptor inhibition in human pancreatic cancer cell lines. Clin Cancer Res 2008; 14:4943-50; PMID:18676769; http://dx.doi.org/10.1158/1078-0432.CCR-08-0436
  • Keirsebilck A, Bonné S, Staes K, van Hengel J, Nollet F, Reynolds A, van Roy F. Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of multiple alternatively spliced isoforms. Genomics 1998; 50:129-46; PMID:9653641; http://dx.doi.org/10.1006/geno.1998.5325
  • Jordan P, Brazao R, Boavida MG, Gespach C, Chastre E. Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors. Oncogene 1999; 18:6835-9; PMID:10597294; http://dx.doi.org/10.1038/sj.onc.1203233
  • Shapiro IM, Cheng AW, Flytzanis NC, Balsamo M, Condeelis JS, Oktay MH, Burge CB, Gertler FB. An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype. PLoS Genet 2011; 7:e1002218; PMID:21876675; http://dx.doi.org/10.1371/journal.pgen.1002218
  • Braeutigam C, Rago L, Rolke A, Waldmeier L, Christofori G, Winter J. The RNA-binding protein Rbfox2: an essential regulator of EMT-driven alternative splicing and a mediator of cellular invasion. Oncogene 2014; 33:1082-92; PMID:23435423; http://dx.doi.org/10.1038/onc.2013.50
  • Warzecha CC, Jiang P, Amirikian K, Dittmar KA, Lu H, Shen S, Guo W, Xing Y, Carstens RP. An ESRP-regulated splicing programme is abrogated during the epithelial-mesenchymal transition. EMBO J 2010; 29:3286-300; PMID:20711167; http://dx.doi.org/10.1038/emboj.2010.195
  • Warzecha CC, Carstens RP. Complex changes in alternative pre-mRNA splicing play a central role in the epithelial-to-mesenchymal transition (EMT). Semin Cancer Biol 2012; 22:417-27; PMID:22548723; http://dx.doi.org/10.1016/j.semcancer.2012.04.003
  • Di Modugno F, Iapicca P, Boudreau A, Mottolese M, Terrenato I, Perracchio L, Carstens RP, Santoni A, Bissell MJ, Nisticò P. Splicing program of human MENA produces a previously undescribed isoform associated with invasive, mesenchymal-like breast tumors. Proc Natl Acad Sci U S A 2012; 109:19280-5; PMID:23129656; http://dx.doi.org/10.1073/pnas.1214394109
  • Solit DB, Rosen N. Towards a unified model of RAF inhibitor resistance. Cancer Discov 2014; 4:27-30; PMID:24402945; http://dx.doi.org/10.1158/2159-8290.CD-13-0961
  • Van Allen EM, Wagle N, Sucker A, Treacy DJ, Johannessen CM, Goetz EM, Place CS, Taylor-Weiner A, Whittaker S, Kryukov GV, et al. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 2014; 4:94-109; PMID:24265153; http://dx.doi.org/10.1158/2159-8290.CD-13-0617
  • Shi H, Hugo W, Kong X, Hong A, Koya RC, Moriceau G, Chodon T, Guo R, Johnson DB, Dahlman KB, et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov 2014; 4:80-93; PMID:24265155; http://dx.doi.org/10.1158/2159-8290.CD-13-0642
  • Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, Atefi M, Titz B, Gabay MT, et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 2011; 480:387-90; PMID:22113612[http://dx.doi.org/10.1038/nature10662
  • Dehm SM, Tindall DJ. Alternatively spliced androgen receptor variants. Endocr Relat Cancer 2011; 18:R183-96; PMID:21778211; http://dx.doi.org/10.1530/ERC-11-0141
  • Li Y, Chan SC, Brand LJ, Hwang TH, Silverstein KA, Dehm SM. Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Res 2013; 73:483-9; PMID:23117885; http://dx.doi.org/10.1158/0008-5472.CAN-12-3630
  • Kole R, Krainer AR, Altman S. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nat Rev Drug Discov 2012; 11:125-40; PMID:22262036
  • Rymond B. Targeting the spliceosome. Nat Chem Biol 2007; 3:533-5; PMID:17710096; http://dx.doi.org/10.1038/nchembio0907-533
  • Chang JG, Yang DM, Chang WH, Chow LP, Chan WL, Lin HH, Huang HD, Chang YS, Hung CH, Yang WK. Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells. PLoS One 2011; 6:e18643; PMID:21694768; http://dx.doi.org/10.1371/journal.pone.0018643
  • Nakajima H, Hori Y, Terano H, Okuhara M, Manda T, Matsumoto S, Shimomura K. New antitumor substances, FR901463, FR901464 and FR901465. II. Activities against experimental tumors in mice and mechanism of action. J Antibiot (Tokyo) 1996; 49:1204-11; PMID:9031665; http://dx.doi.org/10.7164/antibiotics.49.1204
  • Kaida D, Motoyoshi H, Tashiro E, Nojima T, Hagiwara M, Ishigami K, Watanabe H, Kitahara T, Yoshida T, Nakajima H, et al. Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol 2007; 3:576-83; PMID:17643111; http://dx.doi.org/10.1038/nchembio.2007.18
  • Roybal GA, Jurica MS. Spliceostatin A inhibits spliceosome assembly subsequent to prespliceosome formation. Nucleic Acids Res 2010; 38:6664-72; PMID:20529876; http://dx.doi.org/10.1093/nar/gkq494
  • Corrionero A, Minana B, Valcarcel J. Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A. Genes Dev 2011; 25:445-59; PMID:21363963; http://dx.doi.org/10.1101/gad.2014311
  • Convertini P, Shen M, Potter PM, Palacios G, Lagisetti C, de la Grange P, Horbinski C, Fondufe-Mittendorf YN, Webb TR, Stamm S. Sudemycin E influences alternative splicing and changes chromatin modifications. Nucleic Acids Res 2014; 42:4947-61; PMID:24623796; http://dx.doi.org/10.1093/nar/gku151
  • Xiao SH, Manley JL. Phosphorylation of the ASFSF2 RS domain affects both protein-protein and protein-RNA interactions and is necessary for splicing. Genes Dev 1997; 11:334-44; PMID:9030686; http://dx.doi.org/10.1101/gad.11.3.334
  • Cao W, Jamison SF, Garcia-Blanco MA. Both phosphorylation and dephosphorylation of ASFSF2 are required for pre-mRNA splicing in vitro. RNA 1997; 3:1456-67; PMID:9404896
  • Gui JF, Tronchere H, Chandler SD, Fu XD. Purification and characterization of a kinase specific for the serine- and arginine-rich pre-mRNA splicing factors. Proc Natl Acad Sci USA 1994; 91:10824-8; PMID:7526381; http://dx.doi.org/10.1073/pnas.91.23.10824
  • Kuroyanagi N, Onogi H, Wakabayashi T, Hagiwara M. Novel SR-protein-specific kinase, SRPK2, disassembles nuclear speckles. Biochem Biophys Res Commun 1998; 242:357-64; PMID:9446799; http://dx.doi.org/10.1006/bbrc.1997.7913
  • Kojima T, Zama T, Wada K, Onogi H, Hagiwara M. Cloning of human PRP4 reveals interaction with Clk1. J Biol Chem 2001; 276:32247-56; PMID:11418604; http://dx.doi.org/10.1074/jbc.M103790200
  • Rossi F, Labourier E, Forné T, Divita G, Derancourt J, Riou JF, Antoine E, Cathala G, Brunel C, Tazi J. Specific phosphorylation of SR proteins by mammalian DNA topoisomerase I. Nature 1996; 381:80-2; PMID:8609994; http://dx.doi.org/10.1038/381080a0
  • Colwill K, Pawson T, Andrews B, Prasad J, Manley JL, Bell JC, Duncan PI. The ClkSty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution. EMBO J 1996; 15:265-75; PMID:8617202
  • Pilch B, Allemand E, Facompré M, Bailly C, Riou JF, Soret J, Tazi J. Specific inhibition of serine- and arginine-rich splicing factors phosphorylation, spliceosome assembly, and splicing by the antitumor drug NB-506. Cancer Res 2001; 61:6876-84; PMID:11559564
  • Soret J, Bakkour N, Maire S, Durand S, Zekri L, Gabut M, Fic W, Divita G, Rivalle C, Dauzonne D, et al. Selective modification of alternative splicing by indole derivatives that target serine-arginine-rich protein splicing factors. Proc Natl Acad Sci U S A 2005; 102:8764-9; PMID:15939885; http://dx.doi.org/10.1073/pnas.0409829102
  • Muraki M, Ohkawara B, Hosoya T, Onogi H, Koizumi J, Koizumi T, Sumi K, Yomoda J, Murray MV, Kimura H, et al. Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem 2004; 279:24246-54; PMID:15010457; http://dx.doi.org/10.1074/jbc.M314298200
  • Fukuhara T, Hosoya T, Shimizu S, Sumi K, Oshiro T, Yoshinaka Y, Suzuki M, Yamamoto N, Herzenberg LA, Herzenberg LA, et al. Utilization of host SR protein kinases and RNA-splicing machinery during viral replication. Proc Natl Acad Sci U S A 2006; 103:11329-33; PMID:16840555; http://dx.doi.org/10.1073/pnas.0604616103
  • Dominski Z, Kole R. Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides. Proc Natl Acad Sci U S A 1993; 90:8673-7; PMID:8378346; http://dx.doi.org/10.1073/pnas.90.18.8673
  • Bennett CF, Swayze EE. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 2010; 50:259-93; PMID:20055705; http://dx.doi.org/10.1146/annurev.pharmtox.010909.105654
  • Arechavala-Gomeza V, Anthony K, Morgan J, Muntoni F. Antisense oligonucleotide-mediated exon skipping for Duchenne muscular dystrophy: progress and challenges. Curr Gene Ther 2012; 12:152-60; PMID:22533380; http://dx.doi.org/10.2174/156652312800840621
  • Porensky PN, Burghes AH. Antisense oligonucleotides for the treatment of spinal muscular atrophy. Hum Gene Ther 2013; 24:489-98; PMID:23544870; http://dx.doi.org/10.1089/hum.2012.225
  • Rigo F, Hua Y, Krainer AR, Bennett CF. Antisense-based therapy for the treatment of spinal muscular atrophy. J Cell Biol 2012; 199:21-5; PMID:23027901; http://dx.doi.org/10.1083/jcb.201207087
  • Siva K, Covello G, Denti MA. Exon-skipping antisense oligonucleotides to correct missplicing in neurogenetic diseases. Nucleic Acid Ther 2014; 24:69-86; PMID:24506781; http://dx.doi.org/10.1089/nat.2013.0461
  • Ghigna C, De Toledo M, Bonomi S, Valacca C, Gallo S, Apicella M, Eperon I, Tazi J, Biamonti G. Pro-metastatic splicing of Ron proto-oncogene mRNA can be reversed: therapeutic potential of bifunctional oligonucleotides and indole derivatives. RNA Biol 2010; 7:495-503; PMID:20864806; http://dx.doi.org/10.4161/rna.7.4.12744
  • Wang Z, Jeon HY, Rigo F, Bennett CF, Krainer AR. Manipulation of PK-M mutually exclusive alternative splicing by antisense oligonucleotides. Open Biol 2012; 2:120133; PMID:23155487; http://dx.doi.org/10.1098/rsob.120133
  • Shiraishi T, Eysturskarth J, Nielsen PE. Modulation of mdm2 pre-mRNA splicing by 9-aminoacridine-PNA (peptide nucleic acid) conjugates targeting intron-exon junctions. BMC Cancer 2010; 10:342; PMID:20591158; http://dx.doi.org/10.1186/1471-2407-10-342
  • Shieh JJ, Liu KT, Huang SW, Chen YJ, Hsieh TY. Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells. J Invest Dermatol 2009; 129:2497-506; PMID:19369967; http://dx.doi.org/10.1038/jid.2009.83
  • Bruno IG, Jin W, Cote GJ. Correction of aberrant FGFR1 alternative RNA splicing through targeting of intronic regulatory elements. Hum Mol Genet 2004; 13:2409-20; PMID:15333583; http://dx.doi.org/10.1093/hmg/ddh272
  • Mercatante DR, Mohler JL, Kole R. Cellular response to an antisense-mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents. J Biol Chem 2002; 277:49374-82; PMID:12381725; http://dx.doi.org/10.1074/jbc.M209236200
  • Hanamura A, Caceres JF, Mayeda A, Franza BR Jr, Krainer AR. Regulated tissue-specific expression of antagonistic pre-mRNA splicing factors. RNA 1998; 4:430-44; PMID:9630249
  • Zahler AM, Neugebauer KM, Lane WS, Roth MB. Distinct functions of SR proteins in alternative pre-mRNA splicing. Science 1993; 260:219-22; PMID:8385799; http://dx.doi.org/10.1126/science.8385799
  • Chaudhury A, Chander P, Howe PH. Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: Focus on hnRNP E1's multifunctional regulatory roles. RNA 2010; 16:1449-62; PMID:20584894; http://dx.doi.org/10.1261/rna.2254110
  • Han SP, Tang YH, Smith R. Functional diversity of the hnRNPs: past, present and perspectives. Biochem J 2010; 430:379-92; PMID:20795951; http://dx.doi.org/10.1042/BJ20100396
  • Xu X, Yang D, Ding JH, Wang W, Chu PH, Dalton ND, Wang HY, Bermingham JR Jr, Ye Z, Liu F, et al. ASFSF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle. Cell 2005; 120:59-72; PMID:15652482; http://dx.doi.org/10.1016/j.cell.2004.11.036
  • Wang HY, Xu X, Ding JH, Bermingham JR Jr, Fu XD. SC35 plays a role in T cell development and alternative splicing of CD45. Mol Cell 2001; 7:331-42; PMID:11239462; http://dx.doi.org/10.1016/S1097-2765(01)00181-2
  • Jumaa H, Wei G, Nielsen PJ. Blastocyst formation is blocked in mouse embryos lacking the splicing factor SRp20. Curr Biol 1999; 9:899-902; PMID:10469594; http://dx.doi.org/10.1016/S0960-9822(99)80394-7
  • Sen S, Jumaa H, Webster NJ. Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function. Nat Commun 2013; 4:1336; PMID:23299886; http://dx.doi.org/10.1038/ncomms2342
  • Konig J, Zarnack K, Rot G, Curk T, Kayikci M, Zupan B, Turner DJ, Luscombe NM, Ule J. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat Struct Mol Biol 2010; 17:909-15; PMID:20601959; http://dx.doi.org/10.1038/nsmb.1838
  • Ule J, Stefani G, Mele A, Ruggiu M, Wang X, Taneri B, Gaasterland T, Blencowe BJ, Darnell RB. An RNA map predicting Nova-dependent splicing regulation. Nature 2006; 444:580-6; PMID:17065982; http://dx.doi.org/10.1038/nature05304
  • Jangi M, Boutz PL, Paul P, Sharp PA. Rbfox2 controls autoregulation in RNA-binding protein networks. Genes Dev 2014; 28:637-51; PMID:24637117; http://dx.doi.org/10.1101/gad.235770.113
  • Yeo GW, Coufal NG, Liang TY, Peng GE, Fu XD, Gage FH. An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells. Nat Struct Mol Biol 2009; 16:130-7; PMID:19136955; http://dx.doi.org/10.1038/nsmb.1545
  • Xue Y, Zhou Y, Wu T, Zhu T, Ji X, Kwon YS, Zhang C, Yeo G, Black DL, Sun H, et al. Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol Cell 2009; 36:996-1006; PMID:20064465; http://dx.doi.org/10.1016/j.molcel.2009.12.003
  • Sanford JR, Coutinho P, Hackett JA, Wang X, Ranahan W, Caceres JF. Identification of nuclear and cytoplasmic mRNA targets for the shuttling protein SF2ASF. PLoS One 2008; 3:e3369; PMID:18841201; http://dx.doi.org/10.1371/journal.pone.0003369
  • Anko ML, Müller-McNicoll M, Brandl H, Curk T, Gorup C, Henry I, Ule J, Neugebauer KM. The RNA-binding landscapes of two SR proteins reveal unique functions and binding to diverse RNA classes. Genome Biol 2012; 13:R17; PMID:22436691; http://dx.doi.org/10.1186/gb-2012-13-3-r17
  • Rossbach O, Hung LH, Khrameeva E, Schreiner S, König J, Curk T, Zupan B, Ule J, Gelfand MS, Bindereif A. Crosslinking-immunoprecipitation (iCLIP) analysis reveals global regulatory roles of hnRNP L. RNA Biol 2014; 11:146-55; PMID:24526010; http://dx.doi.org/10.4161/rna.27991
  • Huelga SC, Vu AQ, Arnold JD, Liang TY, Liu PP, Yan BY, Donohue JP, Shiue L, Hoon S, Brenner S, et al. Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins. Cell Rep 2012; 1:167-78; PMID:22574288; http://dx.doi.org/10.1016/j.celrep.2012.02.001
  • Rauch J, Ahlemann M, Schaffrik M, Mack B, Ertongur S, Andratschke M, Zeidler R, Lang S, Gires O. Allogenic antibody-mediated identification of head and neck cancer antigens. Biochem Biophys Res Commun 2004; 323:156-62; PMID:15351715; http://dx.doi.org/10.1016/j.bbrc.2004.08.071

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.