Interplay of chromatin modifications and non-coding RNAs in the heart

Figures & data

Table 1. Classification of functional ncRNAs. Transcriptional gene silencing functions of short (grey background) and long ncRNAs by chromatin interaction

ncRNA class	Chromatin interaction
MicroRNA (miRNA)	Yes ^114
Small interfering RNA (siRNA)	Yes ^115
Piwi-interacting RNA (piRNA)	Yes ^116
Small nuclearRNA (snRNA)	Yes ^92
Small nucleolarRNA (snoRNA)	Yes ^117
Natural antisense transcript (NAT)	Yes^80
Large intergenic ncRNA (lincRNA)	Yes^35
Promoter associated RNA (paRNA)	Yes^118
Circular RNA (circRNA)	Yes^78
Enhancer RNA (eRNA)	Yes^119
Pseudogene RNA (trans-NAT)	Yes^120^,^121
Transcribed ultraconserved regions (T-UCRs)	Yes^122
Short-lived RNA transcripts (SLiTs)	Yes^32
Telomeric repeat-containing RNA (TERRA)	Yes^123
Transfer RNA (tRNA)	Not reported
Ribosomal RNA (rRNA)	Not reported

Table 2. Chromatin immunoprecipitation in mouse left ventricle shows specific interaction of EZH2 at genes with bi-directional transcription.

Ink4a, Ink4b, Ak148321/ANRIL

Pax6, Pax6ost1

Nppa, Nppa-as1

Miat, 1700028D13Rik

α-MHC, β-MHC, AS β-MHC

Foxd2, 9130206I24Rik

Hoxc11, Hoxc12, Hotair

Gata3, 4930412O13Rik

Dio3, Dio3os

Ucn, Ucn-as

Islr2, 1600029o15Rik

Dll4, Gm14207

Pou3f3, 2610017I09Rik

2610100L16Rik, Gm10724

Hoxa4, Hoxa5, Hoxa6, Hoxa7, 2700086A05Rik

Irx5, 4933436c20Rik

Fbxo44, Fbxo2

Otx2, Otx2os

H2-K2, AA388235

Pcnxl2, Bc021891

Dlx6, Dlx6as-1

Tbx2, 2610027K06Rik

Myl4 (ALC-1), Myl4-AS

cTn1 (Tnnt3), cTn1-AS

Tgfβ3, Tgfβ3-AS

Listed are genes as enriched by ChIP using antibodies that recognize EZH2 and H3K27me3 modification.⁵² Genes on sense and antisense strands are distinguished by an underline. Significant proportion of the genes enriched by EZH2-ChIP in the mouse heart show specific binding of EZH2 at key cardiac genes with antisense RNA expression. Several cardiac genes with antisense RNA expression including the cardiac regulatory lncRNA genes ANRIL, MIAT, and NPPA-AS appear to be bound by EZH2. Genes encoding non-cardiomyocyte expression programs such as the PAX6, which expresses opposite strand transcript is also repressed by direct binding of EZH2 in the heart. Increased expression of Myosin light chain (MYL4) and TGFβ-3 genes was observed in EZH2 deficient mice,^10,52 both of which are known to express regulatory antisense transcripts, however, show no direct association of EZH2 at these promoters.⁵²

Figure 1. Interplay of chromatin modifications and non-coding RNAs regulate MHC genes in the heart. The expression of cardiac α- and β-MHC genes is regulated in (A) healthy and (B) diseased heart. The bi-directional promoter (bdP) of the α- and β-MHC intergenic region comprises binding sequences for GATA, CTF1/NF1, RAR, T3R, MEF-2 transcription factors. Both the α- and β-MHC genes encode miRNA-208a and miRNA-208b that function in heart health and disease. The bdP is known to transcribe AS β-MHC which serves to regulate β-MHC sense (mRNA) transcription by chromatin interaction. The co-regulatory chromatin determinants BRG1, histone deacetylases (HDACs), and EZH2 are involved in the suppression of AS β-MHC and α-MHC genes in disease.

Table 3. Long ncRNA expression in the heart

Long ncRNA	Cardiac function	Disease association	Expression in disease (↑/↓)	Methods of identification	Mechanism of regulation		Splice variants
ANRIL	Regulation of INK4/ARF locus, genes involved in nuclear and chromatin architecture^56	Cardiac hypertrophy, Atherosclerosis	↑	RNA-ChIP, RACE-PCR, circRNA assays		Chromatin interaction	Reported
cTnI-AS	Regulation of cTnI mRNA^72	Unknown	Unknown	RACE		RNA duplex formation	None reported
NPPA-AS1	Regulation of NPPA mRNA^68	Unknown	Unknown	RACE		RNA duplex formation	Reported
AS-UCN	Regulation of sense transcription/translation^124	Unknown	Unknown	RNase Protection Assay		Overlapping sense transcription	None reported
MIAT or Gomafu	Splicing, Retinal cell fate specification^125	Myocardial Infarction	↑	Northern blot, RACE		Chromatin interaction / Nanog TF binding	Reported
Fendrr	Cardiac mesoderm formation^17	Unknown	Unknown	RACE, RNA-ChIP, ISH		Chromatin interaction	None reported
MHM	Cardiomyocyte Proliferation^126	Cardiac hypertrophy, arrhythmia	Unknown	Northern blot, In Situ hybridization		Chromatin interaction	Reported
H19	Imprinting and Igf2 regulation^65	Hypertrophy & Heart failure	↑	RNA-ChIP, Strand-specific PCR		Chromatin interaction	Reported
91H (AS-H19)	Regulation of Igf2^127	Unknown	Unknown	Strand-specific PCR		Unknown	None reported
Kcnq1ot1	Embryonic heart formation, Regulation of Cdkn1c, KvLQT1 genes^91	Unknown	Unknown	RACE, FISH, RNA-ChIP		Chromatin interaction	Reported
FMR1-AS1 or FMR4	Cell proliferation^128	Proposed	Unknown	RACE, Northern blot		Chromatin interaction proposed	Reported
Air	Embryonic heart formation, Imprinting of Igf2r in adult hearts^129	Unknown	Unknown	RNA-ChIP, FISH		Chromatin interaction	Reported
MLC-ALC-1 antisense	Regulation of MLC-1 mRNA^130	ToF, HOCM	↑	Strand-specific PCR		Unknown	None reported
AS-TGFβ3	Hear chamber formation^131	Unknown	Unknown	RNase protection assay		RISC-mediated silencing proposed	None reported
sONE (AS-eNOS)	eNOS synthesis^132	Unknown	Unknown	Strand-specific PCR, In Situ hybridization		Unknown	None reported
SRA	Myogenesis, SRA proteins synthesis^133	DCM	↓	Strand-specific PCR, Splice variant assays, RNA-ChIP		Chromatin interaction	Reported
AS β-MHC	β-MHC gene transcription^61	Cardiac hypertrophy	↓	Strand-specific PCR		Chromatin interaction	None reported
Braveheart	Cardiovascular lineage commitment^16	Unknown	Unknown	RACE, native RNA-IP		Chromatin interaction	Reported

ANRIL, Antisense non-coding RNA in the INK4 locus; cTnI, Cardiac troponin I; NPPA-AS1, natriuretic peptide precursor A-antisense transcript 1; AS-UCN, Urocortin antisense; MIAT, Myocardial Infarction associated transcript; MHM, Male HyperMethylated; MLC-ALC-1, myosin light chain-atrial light chain-1;AS-TGFβ3, Transforming growth factor β-3 antisense RNA; SRA, steroid receptor RNA activator; ToF, tetrology of fallot; HOCM, Hypertrophic obstructive cardiomyopathy; DCM, dilated cardiomyopathy. RACE, Rapid amplification of cDNA ends; FISH, Fluorescent In Situ Hybridization.

Table 4. Methodologies for the detection, characterization and structural analysis of lncRNA. ncRNA-chromatin interaction assays are highlighted with grey background

Method	Advantage
Strand-specific qRT-PCR	Sense and antisense RNA quantification^71^,^72
ASSAGE	Reveals transcript direction^73
RNA ligation using distinct adaptors	Reveals transcript direction^74
NET-Seq	Transcriptional pausing^87
GRO-Seq	Immediate, transient changes to transcriptome^86
Exon-scanning	Splice variant detection^68^,^79
RACE	Splice variant detection, Obtain full-length transcript sequence^50^,^80
RNA CaptureSeq	Detection of transcripts of low abundance, Novel splice variant detection^82
BRIC-Seq	Transcript stability, RNA decay^32
SAGE (SuperSAGE)	Novel, tissue-specific lncRNA detection^67
PolyA^- RNA-Seq	Identification of bimorphic transcripts and circular RNAs^104
RNA bisulfite conversion	RNA methylation, RNA folding, footprint sequences^73
PTES identification	Splice variants, circular RNA prediction^109
FragSeq	Intra- and inter- RNA base pairing^112
RNaseR assay	Circular transcriptome studies^104^,^107
Native chromatin preparation	Purifies CARs, PolyA^- ncRNAs ^134
RNA-FISH	Cellular compartmentalization of transcripts, chromatin interaction ^89 ^, ^90
RNA-ChIP	Protein-dependent RNA interaction with chromatin ^80
Native RNA-ChIP	Protein-dependent RNA interaction with chromatin ^92
ChIRP	RNA-dependent chromatin interaction ^95
CHART	RNA-dependent chromatin interaction ^96
HITS-CLIP	Cross-linking of directly interacting RNA-protein complexes ^97
PAR-CLIP	Cross-linking of directly interacting RNA-protein complexes ^98

ASSAGE, Asymmetric strand specific analysis of gene expression; GRO-Seq, Global Run-on sequencing; NET-Seq, Native elongating transcript sequencing; RACE, Rapid amplification of cDNA ends; BRIC-Seq, 5’-Bromo-uridine Immunoprecipitation chase-deep sequencing; SAGE, Serial analysis of gene expression; PTES, Post-transcriptional exon scrambling; CARs, Chromatin associated RNAs; FISH, Fluorescent In Situ Hybridization; ChIP, Chromatin immunoprecipitation; ChIRP, Chromatin Isolation by RNA purification; CHART, Capture hybridization analysis of RNA targets; HITS-CLIP, High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation; PAR-CLIP, Photoactivatable-Ribonucleoside-Enhanced crosslinking and immunoprecipitation.

Benhamed M, Herbig U, Ye T, Dejean A, Bischof O. Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells. Nat Cell Biol 2012; 14:266 - 75; http://dx.doi.org/10.1038/ncb2443; PMID: 22366686

 PubMed Web of Science ®Google Scholar

Morris KV, Chan SW, Jacobsen SE, Looney DJ. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 2004; 305:1289 - 92; http://dx.doi.org/10.1126/science.1101372; PMID: 15297624

 PubMed Web of Science ®Google Scholar

Huang XA, Yin H, Sweeney S, Raha D, Snyder M, Lin H. A major epigenetic programming mechanism guided by piRNAs. Dev Cell 2013; 24:502 - 16; http://dx.doi.org/10.1016/j.devcel.2013.01.023; PMID: 23434410

 PubMed Web of Science ®Google Scholar

Mondal T, Rasmussen M, Pandey GK, Isaksson A, Kanduri C. Characterization of the RNA content of chromatin. Genome Res 2010; 20:899 - 907; http://dx.doi.org/10.1101/gr.103473.109; PMID: 20404130

 PubMed Web of Science ®Google Scholar

Schubert T, Pusch MC, Diermeier S, Benes V, Kremmer E, Imhof A, Längst G. Df31 protein and snoRNAs maintain accessible higher-order structures of chromatin. Mol Cell 2012; 48:434 - 44; http://dx.doi.org/10.1016/j.molcel.2012.08.021; PMID: 23022379

 PubMed Web of Science ®Google Scholar

Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, Nagano T, Mancini-Dinardo D, Kanduri C. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 2008; 32:232 - 46; http://dx.doi.org/10.1016/j.molcel.2008.08.022; PMID: 18951091

 PubMed Web of Science ®Google Scholar

Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 2009; 106:11667 - 72; http://dx.doi.org/10.1073/pnas.0904715106; PMID: 19571010

 PubMed Web of Science ®Google Scholar

Han J, Kim D, Morris KV. Promoter-associated RNA is required for RNA-directed transcriptional gene silencing in human cells. Proc Natl Acad Sci U S A 2007; 104:12422 - 7; http://dx.doi.org/10.1073/pnas.0701635104; PMID: 17640892

 PubMed Web of Science ®Google Scholar

Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z, Sharpless NE. Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 2010; 6:e1001233; http://dx.doi.org/10.1371/journal.pgen.1001233; PMID: 21151960

 PubMed Web of Science ®Google Scholar

Melo CA, Drost J, Wijchers PJ, van de Werken H, de Wit E, Oude Vrielink JA, Elkon R, Melo SA, Léveillé N, Kalluri R, et al. eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol Cell 2013; 49:524 - 35; http://dx.doi.org/10.1016/j.molcel.2012.11.021; PMID: 23273978

 PubMed Web of Science ®Google Scholar

Johnsson P, Ackley A, Vidarsdottir L, Lui WO, Corcoran M, Grandér D, Morris KV. A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nat Struct Mol Biol 2013; 20:440 - 6; http://dx.doi.org/10.1038/nsmb.2516; PMID: 23435381

 PubMed Web of Science ®Google Scholar

Hawkins PG, Morris KV. Transcriptional regulation of Oct4 by a long non-coding RNA antisense to Oct4-pseudogene 5. Transcription 2010; 1:165 - 75; http://dx.doi.org/10.4161/trns.1.3.13332; PMID: 21151833

 PubMedGoogle Scholar

Bond AM, Vangompel MJ, Sametsky EA, Clark MF, Savage JC, Disterhoft JF, Kohtz JD. Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry. Nat Neurosci 2009; 12:1020 - 7; http://dx.doi.org/10.1038/nn.2371; PMID: 19620975

 PubMed Web of Science ®Google Scholar

Tani H, Mizutani R, Salam KA, Tano K, Ijiri K, Wakamatsu A, Isogai T, Suzuki Y, Akimitsu N. Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals. Genome Res 2012; 22:947 - 56; http://dx.doi.org/10.1101/gr.130559.111; PMID: 22369889

 PubMed Web of Science ®Google Scholar

Horard B, Gilson E. Telomeric RNA enters the game. Nat Cell Biol 2008; 10:113 - 5; http://dx.doi.org/10.1038/ncb0208-113; PMID: 18246034

 PubMed Web of Science ®Google Scholar

He A, Ma Q, Cao J, von Gise A, Zhou P, Xie H, Zhang B, Hsing M, Christodoulou DC, Cahan P, et al. Polycomb repressive complex 2 regulates normal development of the mouse heart. Circ Res 2012; 110:406 - 15; http://dx.doi.org/10.1161/CIRCRESAHA.111.252205; PMID: 22158708

 PubMed Web of Science ®Google Scholar

Delgado-Olguín P, Huang Y, Li X, Christodoulou D, Seidman CE, Seidman JG, Tarakhovsky A, Bruneau BG. Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis. Nat Genet 2012; 44:343 - 7; http://dx.doi.org/10.1038/ng.1068; PMID: 22267199

 PubMed Web of Science ®Google Scholar

Visel A, Zhu Y, May D, Afzal V, Gong E, Attanasio C, Blow MJ, Cohen JC, Rubin EM, Pennacchio LA. Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature 2010; 464:409 - 12; http://dx.doi.org/10.1038/nature08801; PMID: 20173736

 PubMed Web of Science ®Google Scholar

Voigtsberger S, Bartsch H, Baumann G, Luther HP. Cell type-specific expression of endogenous cardiac Troponin I antisense RNA in the neonatal rat heart. Mol Cell Biochem 2009; 324:1 - 11; http://dx.doi.org/10.1007/s11010-008-9974-3; PMID: 19184367

 PubMed Web of Science ®Google Scholar

Annilo T, Kepp K, Laan M. Natural antisense transcript of natriuretic peptide precursor A (NPPA): structural organization and modulation of NPPA expression. BMC Mol Biol 2009; 10:81; http://dx.doi.org/10.1186/1471-2199-10-81; PMID: 19671135

 PubMed Web of Science ®Google Scholar

Haeger P, Cuevas R, Forray MI, Rojas R, Daza C, Rivadeneira J, Gysling K. Natural expression of immature Ucn antisense RNA in the rat brain. Evidence favoring bidirectional transcription of the Ucn gene locus. Brain Res Mol Brain Res 2005; 139:115 - 28; http://dx.doi.org/10.1016/j.molbrainres.2005.05.024; PMID: 15979199

 PubMedGoogle Scholar

Ishii N, Ozaki K, Sato H, Mizuno H, Saito S, Takahashi A, Miyamoto Y, Ikegawa S, Kamatani N, Hori M, et al. Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J Hum Genet 2006; 51:1087 - 99; http://dx.doi.org/10.1007/s10038-006-0070-9; PMID: 17066261

 PubMed Web of Science ®Google Scholar

Grote P, Wittler L, Hendrix D, Koch F, Währisch S, Beisaw A, Macura K, Bläss G, Kellis M, Werber M, et al. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell 2013; 24:206 - 14; http://dx.doi.org/10.1016/j.devcel.2012.12.012; PMID: 23369715

 PubMed Web of Science ®Google Scholar

Roeszler KN, Itman C, Sinclair AH, Smith CA. The long non-coding RNA, MHM, plays a role in chicken embryonic development, including gonadogenesis. Dev Biol 2012; 366:317 - 26; http://dx.doi.org/10.1016/j.ydbio.2012.03.025; PMID: 22546690

 PubMed Web of Science ®Google Scholar

Lee JH, Gao C, Peng G, Greer C, Ren S, Wang Y, Xiao X. Analysis of transcriptome complexity through RNA sequencing in normal and failing murine hearts. Circ Res 2011; 109:1332 - 41; http://dx.doi.org/10.1161/CIRCRESAHA.111.249433; PMID: 22034492

 PubMed Web of Science ®Google Scholar

Tran VG, Court F, Duputié A, Antoine E, Aptel N, Milligan L, Carbonell F, Lelay-Taha MN, Piette J, Weber M, et al. H19 antisense RNA can up-regulate Igf2 transcription by activation of a novel promoter in mouse myoblasts. PLoS One 2012; 7:e37923; http://dx.doi.org/10.1371/journal.pone.0037923; PMID: 22662250

 PubMedGoogle Scholar

Korostowski L, Sedlak N, Engel N. The Kcnq1ot1 long non-coding RNA affects chromatin conformation and expression of Kcnq1, but does not regulate its imprinting in the developing heart. PLoS Genet 2012; 8:e1002956; http://dx.doi.org/10.1371/journal.pgen.1002956; PMID: 23028363

 PubMedGoogle Scholar

Khalil AM, Faghihi MA, Modarresi F, Brothers SP, Wahlestedt C. A novel RNA transcript with antiapoptotic function is silenced in fragile X syndrome. PLoS One 2008; 3:e1486; http://dx.doi.org/10.1371/journal.pone.0001486; PMID: 18213394

 PubMed Web of Science ®Google Scholar

Sleutels F, Zwart R, Barlow DP. The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 2002; 415:810 - 3; http://dx.doi.org/10.1038/415810a; PMID: 11845212

 PubMed Web of Science ®Google Scholar

Ritter O, Luther HP, Haase H, Baltas LG, Baumann G, Schulte HD, Morano I. Expression of atrial myosin light chains but not alpha-myosin heavy chains is correlated in vivo with increased ventricular function in patients with hypertrophic obstructive cardiomyopathy. J Mol Med (Berl) 1999; 77:677 - 85; http://dx.doi.org/10.1007/s001099900030; PMID: 10569205

 PubMed Web of Science ®Google Scholar

Potts JD, Vincent EB, Runyan RB, Weeks DL. Sense and antisense TGF beta 3 mRNA levels correlate with cardiac valve induction. Dev Dyn 1992; 193:340 - 5; http://dx.doi.org/10.1002/aja.1001930407; PMID: 1511174

 PubMed Web of Science ®Google Scholar

Robb GB, Carson AR, Tai SC, Fish JE, Singh S, Yamada T, Scherer SW, Nakabayashi K, Marsden PA. Post-transcriptional regulation of endothelial nitric-oxide synthase by an overlapping antisense mRNA transcript. J Biol Chem 2004; 279:37982 - 96; http://dx.doi.org/10.1074/jbc.M400271200; PMID: 15234981

 PubMed Web of Science ®Google Scholar

Friedrichs F, Zugck C, Rauch GJ, Ivandic B, Weichenhan D, Müller-Bardorff M, Meder B, El Mokhtari NE, Regitz-Zagrosek V, Hetzer R, et al. HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy. Genome Res 2009; 19:395 - 403; http://dx.doi.org/10.1101/gr.076653.108; PMID: 19064678

 PubMed Web of Science ®Google Scholar

Haddad F, Qin AX, Bodell PW, Zhang LY, Guo H, Giger JM, Baldwin KM. Regulation of antisense RNA expression during cardiac MHC gene switching in response to pressure overload. Am J Physiol Heart Circ Physiol 2006; 290:H2351 - 61; http://dx.doi.org/10.1152/ajpheart.01111.2005; PMID: 16415074

 PubMedGoogle Scholar

Klattenhoff CA, Scheuermann JC, Surface LE, Bradley RK, Fields PA, Steinhauser ML, Ding H, Butty VL, Torrey L, Haas S, et al. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell 2013; 152:570 - 83; http://dx.doi.org/10.1016/j.cell.2013.01.003; PMID: 23352431

 PubMed Web of Science ®Google Scholar

Haddad F, Qin AX, Giger JM, Guo H, Baldwin KM. Potential pitfalls in the accuracy of analysis of natural sense-antisense RNA pairs by reverse transcription-PCR. BMC Biotechnol 2007; 7:21; http://dx.doi.org/10.1186/1472-6750-7-21; PMID: 17480233

 PubMed Web of Science ®Google Scholar

He Y, Vogelstein B, Velculescu VE, Papadopoulos N, Kinzler KW. The antisense transcriptomes of human cells. Science 2008; 322:1855 - 7; http://dx.doi.org/10.1126/science.1163853; PMID: 19056939

 PubMed Web of Science ®Google Scholar

Levin JZ, Yassour M, Adiconis X, Nusbaum C, Thompson DA, Friedman N, Gnirke A, Regev A. Comprehensive comparative analysis of strand-specific RNA sequencing methods. Nat Methods 2010; 7:709 - 15; http://dx.doi.org/10.1038/nmeth.1491; PMID: 20711195

 PubMed Web of Science ®Google Scholar

Churchman LS, Weissman JS. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature 2011; 469:368 - 73; http://dx.doi.org/10.1038/nature09652; PMID: 21248844

 PubMed Web of Science ®Google Scholar

Hah N, Danko CG, Core L, Waterfall JJ, Siepel A, Lis JT, Kraus WL. A rapid, extensive, and transient transcriptional response to estrogen signaling in breast cancer cells. Cell 2011; 145:622 - 34; http://dx.doi.org/10.1016/j.cell.2011.03.042; PMID: 21549415

 PubMed Web of Science ®Google Scholar

Bartsch H, Voigtsberger S, Baumann G, Morano I, Luther HP. Detection of a novel sense-antisense RNA-hybrid structure by RACE experiments on endogenous troponin I antisense RNA. RNA 2004; 10:1215 - 24; http://dx.doi.org/10.1261/rna.5261204; PMID: 15272119

 PubMed Web of Science ®Google Scholar

Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, Lajoie BR, Protacio A, Flynn RA, Gupta RA, et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 2011; 472:120 - 4; http://dx.doi.org/10.1038/nature09819; PMID: 21423168

 PubMed Web of Science ®Google Scholar

Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, Jeddeloh JA, Mattick JS, Rinn JL. Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat Biotechnol 2012; 30:99 - 104; http://dx.doi.org/10.1038/nbt.2024; PMID: 22081020

 PubMed Web of Science ®Google Scholar

Gibb EA, Vucic EA, Enfield KS, Stewart GL, Lonergan KM, Kennett JY, Becker-Santos DD, MacAulay CE, Lam S, Brown CJ, et al. Human cancer long non-coding RNA transcriptomes. PLoS One 2011; 6:e25915; http://dx.doi.org/10.1371/journal.pone.0025915; PMID: 21991387

 PubMed Web of Science ®Google Scholar

Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One 2012; 7:e30733; http://dx.doi.org/10.1371/journal.pone.0030733; PMID: 22319583

 PubMed Web of Science ®Google Scholar

Al-Balool HH, Weber D, Liu Y, Wade M, Guleria K, Nam PL, Clayton J, Rowe W, Coxhead J, Irving J, et al. Post-transcriptional exon shuffling events in humans can be evolutionarily conserved and abundant. Genome Res 2011; 21:1788 - 99; http://dx.doi.org/10.1101/gr.116442.110; PMID: 21948523

 PubMed Web of Science ®Google Scholar

Underwood JG, Uzilov AV, Katzman S, Onodera CS, Mainzer JE, Mathews DH, Lowe TM, Salama SR, Haussler D. FragSeq: transcriptome-wide RNA structure probing using high-throughput sequencing. Nat Methods 2010; 7:995 - 1001; http://dx.doi.org/10.1038/nmeth.1529; PMID: 21057495

 PubMed Web of Science ®Google Scholar

Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013; 495:333 - 8; http://dx.doi.org/10.1038/nature11928; PMID: 23446348

 PubMed Web of Science ®Google Scholar

Rodríguez-Campos A, Azorín F. RNA is an integral component of chromatin that contributes to its structural organization. PLoS One 2007; 2:e1182; http://dx.doi.org/10.1371/journal.pone.0001182; PMID: 18000552

 PubMed Web of Science ®Google Scholar

Chureau C, Chantalat S, Romito A, Galvani A, Duret L, Avner P, Rougeulle C. Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region. Hum Mol Genet 2011; 20:705 - 18; http://dx.doi.org/10.1093/hmg/ddq516; PMID: 21118898

 PubMed Web of Science ®Google Scholar

Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell 2010; 39:925 - 38; http://dx.doi.org/10.1016/j.molcel.2010.08.011; PMID: 20797886

 PubMed Web of Science ®Google Scholar

Chu C, Qu K, Zhong FL, Artandi SE, Chang HY. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell 2011; 44:667 - 78; http://dx.doi.org/10.1016/j.molcel.2011.08.027; PMID: 21963238

 PubMed Web of Science ®Google Scholar

Simon MD, Wang CI, Kharchenko PV, West JA, Chapman BA, Alekseyenko AA, Borowsky ML, Kuroda MI, Kingston RE. The genomic binding sites of a noncoding RNA. Proc Natl Acad Sci U S A 2011; 108:20497 - 502; http://dx.doi.org/10.1073/pnas.1113536108; PMID: 22143764

 PubMed Web of Science ®Google Scholar

Ule J, Jensen KB, Ruggiu M, Mele A, Ule A, Darnell RB. CLIP identifies Nova-regulated RNA networks in the brain. Science 2003; 302:1212 - 5; http://dx.doi.org/10.1126/science.1090095; PMID: 14615540

 PubMed Web of Science ®Google Scholar

Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M Jr., Jungkamp AC, Munschauer M, et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 2010; 141:129 - 41; http://dx.doi.org/10.1016/j.cell.2010.03.009; PMID: 20371350

 PubMed Web of Science ®Google Scholar