Concentration and Localization of Coexpressed ELAV/Hu Proteins Control Specificity of mRNA Processing

REFERENCES

• Glisovic T, Bachorik JL, Yong J, Dreyfuss G. 2008. RNA-binding proteins and post-transcriptional gene regulation. FEBS Lett 582:1977–1986. http://dx.doi.org/10.1016/j.febslet.2008.03.004.
   PubMed Web of Science ®Google Scholar
• Keene JD. 2007. RNA regulons: coordination of post-transcriptional events. Nat Rev Genet 8:533–543. http://dx.doi.org/10.1038/nrg2111.
   PubMed Web of Science ®Google Scholar
• Darnell RB. 2013. RNA protein interaction in neurons. Annu Rev Neurosci 36:243–270. http://dx.doi.org/10.1146/annurev-neuro-062912-114322.
   PubMed Web of Science ®Google Scholar
• Soller M. 2006. Pre-messenger RNA processing and its regulation: a genomic perspective. Cell Mol Life Sci 63:796–819. http://dx.doi.org/10.1007/s00018-005-5391-x.
   PubMedGoogle Scholar
• Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat LH, Dale RK, Smith SA, Yarosh CA, Kelly SM, Nabet B, Mecenas D, Li W, Laishram RS, Qiao M, Lipshitz HD, Piano F, Corbett AH, Carstens RP, Frey BJ, Anderson RA, Lynch KW, Penalva LO, Lei EP, Fraser AG, Blencowe BJ, Morris QD, Hughes TR. 2013. A compendium of RNA-binding motifs for decoding gene regulation. Nature 499:172–177. http://dx.doi.org/10.1038/nature12311.
   PubMed Web of Science ®Google Scholar
• Kafri R, Springer M, Pilpel Y. 2009. Genetic redundancy: new tricks for old genes. Cell 136:389–392. http://dx.doi.org/10.1016/j.cell.2009.01.027.
   PubMedGoogle Scholar
• Hinman MN, Lou H. 2008. Diverse molecular functions of Hu proteins. Cell Mol Life Sci 65:3168–3181. http://dx.doi.org/10.1007/s00018-008-8252-6.
   PubMed Web of Science ®Google Scholar
• Soller M, White K. 2004. ELAV. Curr Biol 14:R53. http://dx.doi.org/10.1016/j.cub.2003.12.041.
   PubMedGoogle Scholar
• Samson ML. 2008. Rapid functional diversification in the structurally conserved ELAV family of neuronal RNA binding proteins. BMC Genomics 9:392. http://dx.doi.org/10.1186/1471-2164-9-392.
   PubMed Web of Science ®Google Scholar
• Okano HJ, Darnell RB. 1997. A hierarchy of Hu RNA binding proteins in developing and adult neurons. J Neurosci 17:3024–3037.
   PubMedGoogle Scholar
• Kim YJ, Baker BS. 1993. The Drosophila gene rbp9 encodes a protein that is a member of a conserved group of putative RNA binding proteins that are nervous system-specific in both flies and humans. J Neurosci 13:1045–1056.
   PubMed Web of Science ®Google Scholar
• Samson ML, Chalvet F. 2003. found in neurons, a third member of the Drosophila elav gene family, encodes a neuronal protein and interacts with elav. Mech Dev 120:373–383. http://dx.doi.org/10.1016/S0925-4773(02)00444-6.
   PubMed Web of Science ®Google Scholar
• Yao K-M, Samson M-L, Reeves R, White K. 1993. Gene elav of Drosophila melanogaster: a prototype for neuronal-specific RNA binding protein gene family that is conserved in flies and humans. J Neurobiol 24:723–739. http://dx.doi.org/10.1002/neu.480240604.
   PubMedGoogle Scholar
• Schutt C, Nothiger R. 2000. Structure, function and evolution of sex-determining systems in Dipteran insects. Development 127:667–677.
   PubMed Web of Science ®Google Scholar
• Koushika SP, Lisbin MJ, White K. 1996. ELAV, a Drosophila neuron-specific protein, mediates the generation of an alternatively spliced neural protein isoform. Curr Biol 6:1634–1641. http://dx.doi.org/10.1016/S0960-9822(02)70787-2.
   PubMed Web of Science ®Google Scholar
• Koushika SP, Soller M, White K. 2000. The neuron-enriched splicing pattern of Drosophila erect wing is dependent on the presence of ELAV protein. Mol Cell Biol 20:1836–1845. http://dx.doi.org/10.1128/MCB.20.5.1836-1845.2000.
   PubMed Web of Science ®Google Scholar
• Lisbin MJ, Qiu J, White K. 2001. The neuron-specific RNA-binding protein ELAV regulates neuroglian alternative splicing in neurons and binds directly to its pre-mRNA. Genes Dev 15:2546–2561. http://dx.doi.org/10.1101/gad.903101.
   PubMed Web of Science ®Google Scholar
• Rogulja-Ortmann A, Picao-Osorio J, Villava C, Patraquim P, Lafuente E, Aspden J, Thomsen S, Technau GM, Alonso CR. 2014. The RNA-binding protein ELAV regulates Hox RNA processing, expression and function within the Drosophila nervous system. Development 141:2046–2056. http://dx.doi.org/10.1242/dev.101519.
   PubMed Web of Science ®Google Scholar
• Simionato E, Barrios N, Duloquin L, Boissonneau E, Lecorre P, Agnes F. 2007. The Drosophila RNA-binding protein ELAV is required for commissural axon midline crossing via control of commissureless mRNA expression in neurons. Dev Biol 301:166–177. http://dx.doi.org/10.1016/j.ydbio.2006.09.028.
   PubMed Web of Science ®Google Scholar
• Soller M, White K. 2003. ELAV inhibits 3′-end processing to promote neural splicing of ewg pre-mRNA. Genes Dev 17:2526–2538. http://dx.doi.org/10.1101/gad.1106703.
   PubMed Web of Science ®Google Scholar
• Toba G, Qui J, Koushika SP, White K. 2002. Ectopic expression of Drosophila ELAV and human HuD in Drosophila wing disc cells reveals functional distinctions and similarities. J Cell Sci 115:2413–2421.
   PubMedGoogle Scholar
• Antic D, Lu N, Keene JD. 1999. ELAV tumor antigen, hel-N1, increases translation of neurofilament M mRNA and induces formation of neurites in human teratocarcinoma cells. Genes Dev 13:449–461. http://dx.doi.org/10.1101/gad.13.4.449.
   PubMedGoogle Scholar
• Brennan CM, Steitz JA. 2001. HuR and mRNA stability. Cell Mol Life Sci 58:266–277. http://dx.doi.org/10.1007/PL00000854.
   PubMed Web of Science ®Google Scholar
• Ince-Dunn G, Okano HJ, Jensen KB, Park WY, Zhong R, Ule J, Mele A, Fak JJ, Yang C, Zhang C, Yoo J, Herre M, Okano H, Noebels JL, Darnell RB. 2012. Neuronal Elav-like (Hu) proteins regulate RNA splicing and abundance to control glutamate levels and neuronal excitability. Neuron 75:1067–1080. http://dx.doi.org/10.1016/j.neuron.2012.07.009.
   PubMed Web of Science ®Google Scholar
• Lebedeva S, Jens M, Theil K, Schwanhausser B, Selbach M, Landthaler M, Rajewsky N. 2011. Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol Cell 43:340–352. http://dx.doi.org/10.1016/j.molcel.2011.06.008.
   PubMed Web of Science ®Google Scholar
• Mukherjee N, Corcoran DL, Nusbaum JD, Reid DW, Georgiev S, Hafner M, Ascano M, Jr, Tuschl T, Ohler U, Keene JD. 2011. Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability. Mol Cell 43:327–339. http://dx.doi.org/10.1016/j.molcel.2011.06.007.
   PubMed Web of Science ®Google Scholar
• Uren PJ, Burns SC, Ruan J, Singh KK, Smith AD, Penalva LO. 2011. Genomic analyses of the RNA-binding protein Hu antigen R (HuR) identify a complex network of target genes and novel characteristics of its binding sites. J Biol Chem 286:37063–37066. http://dx.doi.org/10.1074/jbc.C111.266882.
   PubMed Web of Science ®Google Scholar
• Zhu H, Hinman MN, Hasman RA, Mehta P, Lou H. 2008. Regulation of neuron-specific alternative splicing of neurofibromatosis type 1 pre-mRNA. Mol Cell Biol 28:1240–1251. http://dx.doi.org/10.1128/MCB.01509-07.
   PubMed Web of Science ®Google Scholar
• Zhu H, Zhou HL, Hasman RA, Lou H. 2007. Hu proteins regulate polyadenylation by blocking sites containing U-rich sequences. J Biol Chem 282:2203–2210. http://dx.doi.org/10.1074/jbc.M609349200.
   PubMed Web of Science ®Google Scholar
• Fan XC, Steitz JA. 1998. Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. EMBO J 17:3448–3460. http://dx.doi.org/10.1093/emboj/17.12.3448.
   PubMed Web of Science ®Google Scholar
• Campos A-R, Grossman D, White K. 1985. Mutant alleles at the locus elav in Drosophila melanogaster lead to nervous system defects. A developmental-genetic analysis. . J Neurogenet 2:197–218.
   PubMed Web of Science ®Google Scholar
• Haussmann IU, White K, Soller M. 2008. Erect wing regulates synaptic growth in Drosophila by integration of multiple signaling pathways. Genome Biol 9:R73. http://dx.doi.org/10.1186/gb-2008-9-4-r73.
   PubMed Web of Science ®Google Scholar
• Zanini D, Jallon JM, Rabinow L, Samson ML. 2012. Deletion of the Drosophila neuronal gene found in neurons disrupts brain anatomy and male courtship. Genes Brain Behav 11:819–827. http://dx.doi.org/10.1111/j.1601-183X.2012.00817.x.
   PubMed Web of Science ®Google Scholar
• Kim J, Kim YJ, Kim-Ha J. 2010. Blood-brain barrier defects associated with Rbp9 mutation. Mol Cells 29:93–98. http://dx.doi.org/10.1007/s10059-010-0040-0.
   PubMed Web of Science ®Google Scholar
• Toba G, Yamamoto D, White K. 2010. Life-span phenotypes of elav and Rbp9 in Drosophila suggest functional cooperation of the two ELAV-family protein genes. Arch Insect Biochem Physiol 74:261–265. http://dx.doi.org/10.1002/arch.20377.
   PubMedGoogle Scholar
• Soller M, White K. 2005. ELAV multimerizes on conserved AU4-6 motifs important for ewg splicing regulation. Mol Cell Biol 25:7580–7591. http://dx.doi.org/10.1128/MCB.25.17.7580-7591.2005.
   PubMed Web of Science ®Google Scholar
• Parks AL, Cook KR, Belvin M, Dompe NA, Fawcett R, Huppert K, Tan LR, Winter CG, Bogart KP, Deal JE, Deal-Herr ME, Grant D, Marcinko M, Miyazaki WY, Robertson S, Shaw KJ, Tabios M, Vysotskaia V, Zhao L, Andrade RS, Edgar KA, Howie E, Killpack K, Milash B, Norton A, Thao D, Whittaker K, Winner MA, Friedman L, Margolis J, Singer MA, Kopczynski C, Curtis D, Kaufman TC, Plowman GD, Duyk G, Francis-Lang HL. 2004. Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nat Genet 36:288–292. http://dx.doi.org/10.1038/ng1312.
   PubMed Web of Science ®Google Scholar
• Thibault ST, Singer MA, Miyazaki WY, Milash B, Dompe NA, Singh CM, Buchholz R, Demsky M, Fawcett R, Francis-Lang HL, Ryner L, Cheung LM, Chong A, Erickson C, Fisher WW, Greer K, Hartouni SR, Howie E, Jakkula L, Joo D, Killpack K, Laufer A, Mazzotta J, Smith RD, Stevens LM, Stuber C, Tan LR, Ventura R, Woo A, Zakrajsek I, Zhao L, Chen F, Swimmer C, Kopczynski C, Duyk G, Winberg ML, Margolis J. 2004. A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac. Nat Genet 36:283–287. http://dx.doi.org/10.1038/ng1314.
   PubMed Web of Science ®Google Scholar
• Stowers RS, Schwarz TL. 1999. A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype. Genetics 152:1631–1639.
   PubMedGoogle Scholar
• Haussmann IU, Li M, Soller M. 2011. ELAV-mediated 3′-end processing of ewg transcripts is evolutionarily conserved despite sequence degeneration of the ELAV-binding site. Genetics 189:97–107. http://dx.doi.org/10.1534/genetics.111.131383.
   PubMedGoogle Scholar
• Kraus ME, Lis JT. 1994. The concentration of B52, an essential splicing factor and regulator of splice site choice in vitro, is critical for Drosophila development. Mol Cell Biol 14:5360–5370.
   PubMedGoogle Scholar
• Quinn LM, Dickins RA, Coombe M, Hime GR, Bowtell DD, Richardson H. 2004. Drosophila Hfp negatively regulates dmyc and stg to inhibit cell proliferation. Development 131:1411–1423. http://dx.doi.org/10.1242/dev.01019.
   PubMedGoogle Scholar
• Samuels ME, Bopp D, Colvin RA, Roscigno RF, Garcia-Blanco MA, Schedl P. 1994. RNA binding by Sxl proteins in vitro and in vivo. Mol Cell Biol 14:4975–4990.
   PubMedGoogle Scholar
• Yannoni YM, White K. 1999. Domain necessary for Drosophila ELAV nuclear localization: function requires nuclear ELAV. J Cell Sci 112:4501–4512.
   PubMedGoogle Scholar
• Koushika SP, Soller M, DeSimone SM, Daub DM, White K. 1999. Differential and inefficient splicing of a broadly expressed Drosophila erect wing transcript results in tissue-specific enrichment of the vital EWG protein isoform. Mol Cell Biol 19:3998–4007.
   PubMedGoogle Scholar
• Lisbin MJ, Gordon M, Yannoni YM, White K. 2000. Function of RRM domains of Drosophila melanogaster ELAV: RNP1 mutations and RRM domain replacements with ELAV family proteins and SXL. Genetics 155:1789–1798.
   PubMed Web of Science ®Google Scholar
• Soller M, Haussmann IU, Hollmann M, Choffat Y, White K, Kubli E, Schafer MA. 2006. Sex-peptide-regulated female sexual behavior requires a subset of ascending ventral nerve cord neurons. Curr Biol 16:1771–1782. http://dx.doi.org/10.1016/j.cub.2006.07.055.
   PubMedGoogle Scholar
• Toba G, White K. 2008. The third RNA recognition motif of Drosophila ELAV protein has a role in multimerization. Nucleic Acids Res 36:1390–1399. http://dx.doi.org/10.1093/nar/gkm1168.
   PubMed Web of Science ®Google Scholar
• Preibisch S, Saalfeld S, Tomancak P. 2009. Globally optimal stitching of tiled 3D microscopic image acquisitions. Bioinformatics 25:1463–1465. http://dx.doi.org/10.1093/bioinformatics/btp184.
   PubMed Web of Science ®Google Scholar
• Coulom H, Birman S. 2004. Chronic exposure to rotenone models sporadic Parkinson's disease in Drosophila melanogaster. J Neurosci 24:10993–10998. http://dx.doi.org/10.1523/JNEUROSCI.2993-04.2004.
   PubMed Web of Science ®Google Scholar
• Kim-Ha J, Kim J, Kim YJ. 1999. Requirement of RBP9, a Drosophila Hu homolog, for regulation of cystocyte differentiation and oocyte determination during oogenesis. Mol Cell Biol 19:2505–2514.
   PubMed Web of Science ®Google Scholar
• Haussmann IU, Soller M. 2010. Differential activity of EWG transcription factor isoforms identifies a subset of differentially regulated genes important for synaptic growth regulation. Dev Biol 348:224–230. http://dx.doi.org/10.1016/j.ydbio.2010.09.006.
   PubMedGoogle Scholar
• Soller M, Li M, Haussmann IU. 2008. Regulation of the ELAV target ewg: insights from an evolutionary perspective. Biochem Soc Trans 36:502–504. http://dx.doi.org/10.1042/BST0360502.
   PubMedGoogle Scholar
• Bopp D, Saccone G, Beye M. 2014. Sex determination in insects: variations on a common theme. Sex Dev 8:20–28. http://dx.doi.org/10.1159/000356458.
   PubMedGoogle Scholar
• Salz HK. 2011. Sex determination in insects: a binary decision based on alternative splicing. Curr Opin Genet Dev 21:395–400. http://dx.doi.org/10.1016/j.gde.2011.03.001.
   PubMed Web of Science ®Google Scholar
• Wang J, Bell LR. 1994. The Sex-lethal amino terminus mediates cooperative interactions in RNA binding and is essential for splicing regulation. Genes Dev 8:2072–2085. http://dx.doi.org/10.1101/gad.8.17.2072.
   PubMedGoogle Scholar
• Rideout EJ, Dornan AJ, Neville MC, Eadie S, Goodwin SF. 2010. Control of sexual differentiation and behavior by the doublesex gene in Drosophila melanogaster. Nat Neurosci 13:458–466. http://dx.doi.org/10.1038/nn.2515.
   PubMed Web of Science ®Google Scholar
• Labourier E, Bourbon HM, Gallouzi IE, Fostier M, Allemand E, Tazi J. 1999. Antagonism between RSF1 and SR proteins for both splice-site recognition in vitro and Drosophila development. Genes Dev 13:740–753. http://dx.doi.org/10.1101/gad.13.6.740.
   PubMedGoogle Scholar
• Ehrmann I, Dalgliesh C, Liu Y, Danilenko M, Crosier M, Overman L, Arthur HM, Lindsay S, Clowry GJ, Venables JP, Fort P, Elliott DJ. 2013. The tissue-specific RNA binding protein T-STAR controls regional splicing patterns of neurexin pre-mRNAs in the brain. PLoS Genet 9:e1003474. http://dx.doi.org/10.1371/journal.pgen.1003474.
   PubMed Web of Science ®Google Scholar
• Qi J, Su S, McGuffin ME, Mattox W. 2006. Concentration dependent selection of targets by an SR splicing regulator results in tissue-specific RNA processing. Nucleic Acids Res 34:6256–6263. http://dx.doi.org/10.1093/nar/gkl755.
   PubMedGoogle Scholar
• Venables JP, Bourgeois CF, Dalgliesh C, Kister L, Stevenin J, Elliott DJ. 2005. Up-regulation of the ubiquitous alternative splicing factor Tra2β causes inclusion of a germ cell-specific exon. Hum Mol Genet 14:2289–2303. http://dx.doi.org/10.1093/hmg/ddi233.
   PubMed Web of Science ®Google Scholar
• Caceres JF, Stamm S, Helfman DM, Krainer AR. 1994. Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors. Science 265:1706–1709. http://dx.doi.org/10.1126/science.8085156.
   PubMed Web of Science ®Google Scholar
• Chen M, David CJ, Manley JL. 2012. Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins. Nat Struct Mol Biol 19:346–354. http://dx.doi.org/10.1038/nsmb.2219.
   PubMed Web of Science ®Google Scholar
• Hilgers V, Perry MW, Hendrix D, Stark A, Levine M, Haley B. 2011. Neural-specific elongation of 3′ UTRs during Drosophila development. Proc Natl Acad Sci U S A 108:15864–15869. http://dx.doi.org/10.1073/pnas.1112672108.
   PubMed Web of Science ®Google Scholar
• Samson ML. 1998. Evidence for 3′ untranslated region-dependent autoregulation of the Drosophila gene encoding the neuronal nuclear RNA-binding protein ELAV. Genetics 150:723–733.
   PubMed Web of Science ®Google Scholar
• Bronicki LM, Jasmin BJ. 2013. Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction. RNA 19:1019–1037. http://dx.doi.org/10.1261/rna.039164.113.
   PubMed Web of Science ®Google Scholar
• Hilgers V, Lemke SB, Levine M. 2012. ELAV mediates 3′ UTR extension in the Drosophila nervous system. Genes Dev 26:2259–2264. http://dx.doi.org/10.1101/gad.199653.112.
   PubMed Web of Science ®Google Scholar
• Wang H, Molfenter J, Zhu H, Lou H. 2010. Promotion of exon 6 inclusion in HuD pre-mRNA by Hu protein family members. Nucleic Acids Res 38:3760–3770. http://dx.doi.org/10.1093/nar/gkq028.
   PubMedGoogle Scholar
• Brauer U, Zaharieva E, Soller M. 2014. Regulation of ELAV/Hu RNA-binding proteins by phosphorylation. Biochem Soc Trans 42:1147–1151. http://dx.doi.org/10.1042/BST20140103.
   PubMedGoogle Scholar
• Akamatsu W, Fujihara H, Mitsuhashi T, Yano M, Shibata S, Hayakawa Y, Okano HJ, Sakakibara S, Takano H, Takano T, Takahashi T, Noda T, Okano H. 2005. The RNA-binding protein HuD regulates neuronal cell identity and maturation. Proc Natl Acad Sci U S A 102:4625–4630. http://dx.doi.org/10.1073/pnas.0407523102.
   PubMedGoogle Scholar
• Ule J, Stefani G, Mele A, Ruggiu M, Wang X, Taneri B, Gaasterland T, Blencowe BJ, Darnell RB. 2006. An RNA map predicting Nova-dependent splicing regulation. Nature 444:580–586. http://dx.doi.org/10.1038/nature05304.
   PubMed Web of Science ®Google Scholar
• Pascale A, Gusev PA, Amadio M, Dottorini T, Govoni S, Alkon DL, Quattrone A. 2004. Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory. Proc Natl Acad Sci U S A 101:1217–1222. http://dx.doi.org/10.1073/pnas.0307674100.
   PubMed Web of Science ®Google Scholar
• Kornblihtt AR. 2005. Promoter usage and alternative splicing. Curr Opin Cell Biol 17:262–268. http://dx.doi.org/10.1016/j.ceb.2005.04.014.
   PubMed Web of Science ®Google Scholar
• Oktaba K, Zhang W, Lotz TS, Jun DJ, Lemke SB, Ng SP, Esposito E, Levine M, Hilgers V. 2015. ELAV links paused Pol II to alternative polyadenylation in the Drosophila nervous system. Mol Cell 57:341–348. http://dx.doi.org/10.1016/j.molcel.2014.11.024.
   PubMedGoogle Scholar
• Cooper TA, Wan L, Dreyfuss G. 2009. RNA and disease. Cell 136:777–793. http://dx.doi.org/10.1016/j.cell.2009.02.011.
   PubMed Web of Science ®Google Scholar
• David CJ, Manley JL. 2010. Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev 24:2343–2364. http://dx.doi.org/10.1101/gad.1973010.
   PubMed Web of Science ®Google Scholar