Abstract
Posttranscriptional regulation comprises those mechanisms occurring after the initial copy of the DNA sequence is transcribed into an intermediate RNA molecule (i.e., messenger RNA) until such a molecule is used as a template to generate a protein. A subset of these posttranscriptional regulatory mechanisms essentially are destined to process the immature mRNA toward its mature form, conferring the adequate mRNA stability, providing the means for pertinent introns excision, and controlling mRNA turnover rate and quality control check. An additional layer of complexity is added in certain cases, since discrete nucleotide modifications in the mature RNA molecule are added by RNA editing, a process that provides large mature mRNA diversity. Moreover, a number of posttranscriptional regulatory mechanisms occur in a cell- and tissue-specific manner, such as alternative splicing and non-coding RNA-mediated regulation. In this chapter we will briefly summarize current state-of-the-art knowledge of general posttranscriptional mechanisms, while major emphases will be devoted to those tissue-specific posttranscriptional modifications that impact on cardiac development and congenital heart disease.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Lukong KE, Chang KW, Khandjian EW et al (2008) RNA-binding proteins in human genetic disease. Trends Genet 24:416–425
Blech-Hermoni Y, Ladd AN (2013) RNA binding proteins in the regulation of heart development. Int J Biochem Cell Biol 45:2467–2478
Forget A, Chartrand P (2011) Cotranscriptional assembly of mRNP complexes that determine the cytoplasmic fate of mRNA. Transcription 2:86–90
Fresco LD, Buratowski S (1996) Conditional mutants of the yeast mRNA capping enzyme show that the cap enhances, but is not required for, mRNA splicing. RNA 2:584–596
Shatkin AJ, Manley JL (2000) The ends of the affair: capping and polyadenylation. Nat Struct Biol 7:838–842
Glover-Cutter K, Kim S, Espinosa J et al (2008) RNA polymerase II pauses and associates with pre-mRNA processing factors at both ends of genes. Nat Struct Mol Biol 15:71–78
Cowling VH (2009) Regulation of mRNA cap methylation. Biochem J 425:295–302
Suh MH, Meyer PA, Gu M et al (2010) A dual interface determines the recognition of RNA polymerase II by RNA capping enzyme. J Biol Chem 285:34027–34038
Yue Z, Maldonado E, Pillutla R et al (1997) Mammalian capping enzyme complements mutant Saccharomyces cerevisiae lacking mRNA guanylyltransferase and selectively binds the elongating form of RNA polymerase II. Proc Natl Acad Sci U S A 94:12898–12903
Tsukamoto T, Shibagaki Y, Niikura Y et al (1998) Cloning and characterization of three human cDNAs encoding mRNA (guanine-7-)-methyltransferase, an mRNA cap methylase. Biochem Biophys Res Commun 251:27–34
Yamada-Okabe T, Doi R, Shimmi O et al (1998) Isolation and characterization of a human cDNA for mRNA 5′-capping enzyme. Nucleic Acids Res 26:1700–1706
Pillutla RC, Shimamoto A, Furuichi Y et al (1998) Human mRNA capping enzyme (RNGTT) and cap methyltransferase (RNMT) map to 6q16 and 18p11.22-p11.23, respectively. Genomics 1998(54):351–353
Ishikawa K, Nagase T, Nakajima D et al (1997) Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro. DNA Res 4:307–313
Konarska MM, Padgett RA, Sharp PA (1984) Recognition of cap structure in splicing in vitro of mRNA precursors. Cell 38:731–736
Spriggs KA, Stoneley M, Bushell M et al (2008) Re-programming of translation following cell stress allows IRES-mediated translation to predominate. Biol Cell 100:27–38
Furuichi Y, LaFiandra A, Shatkin AJ (1977) 5′-Terminal structure and mRNA stability. Nature 266:235–239
Shimotohno K, Kodama Y, Hashimoto J et al (1977) Importance of 5′-terminal blocking structure to stabilize mRNA in eukaryotic protein synthesis. Proc Natl Acad Sci U S A 74:2734–2738
Murthy KG, Park P, Manley JL (1991) A nuclear micrococcal-sensitive, ATP-dependent exoribonuclease degrades uncapped but not capped RNA substrates. Nucleic Acids Res 19:2685–2692
Schwer B, Shuman S (1996) Conditional inactivation of mRNA capping enzyme affects yeast pre-mRNA splicing in vivo. RNA 2:574–583
Schwer B, Mao X, Shuman S (1998) Accelerated mRNA decay in conditional mutants of yeast mRNA capping enzyme. Nucleic Acids Res 26:2050–2057
Flaherty SM, Fortes P, Izaurralde E et al (1997) Participation of the nuclear cap binding complex in pre-mRNA 3′ processing. Proc Natl Acad Sci U S A 94:11893–11898
Curinha A, Braz SO, Pereira-Castro I et al (2014) Implications of polyadenylation in health and disease. Nucleus 5:508–519
Tian B, Hu J, Zhang H, Lutz CS (2005) A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Res 33:201–212
Pelechano V, Wei W, Steinmetz LM (2013) Extensive transcriptional heterogeneity revealed by isoform profiling. Nature 497:127–131
Carpenter S, Ricci EP, Mercier BC et al (2014) Post-transcriptional regulation of gene expression in innate immunity. Nat Rev Immunol 14:361–376
Griseri P, Pagès G (2014) Regulation of the mRNA half-life in breast cancer. World J Clin Oncol 5:323–334
Chatterjee S, Pal JK (2009) Role of 5′- and 3′-untranslated regions of mRNAs in human diseases. Biol Cell 101:251–262
Rehfeld A, Plass M, Krogh A et al (2013) Alterations in polyadenylation and its implications for endocrine disease. Front Endocrinol 4:53
Lewis BP, Green RE, Brenner SE (2003) Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans. Proc Natl Acad Sci U S A 100:189–192
Pan Q, Saltzman AL, Kim YK et al (2006) Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression. Genes Dev 20:153–158
Mendell JT, Sharifi NA, Meyers JL et al (2004) Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat Genet 36:1073–1078
Wittmann J, Hol EM, Jäck HM (2006) hUPF2 silencing identifies physiologic substrates of mammalian nonsense-mediated mRNA decay. Mol Cell Biol 26:1272–1287
Ni JZ, Grate L, Donohue JP et al (2007) Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay. Genes Dev 21:708–718
Chang YF, Imam JS, Wilkinson MF (2007) The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 76:51–74
Maquat LE (2005) Nonsense-mediated mRNA decay in mammals. J Cell Sci 118:1773–1776
Garneau NL, Wilusz J, Wilusz CJ (2007) The highways and byways of mRNA decay. Nat Rev Mol Cell Biol 8:113–126
Ishigaki Y, Li X, Serin G, Maquat LE (2001) Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell 106:607–617
Lejeune F, Ishigaki Y, Li X, Maquat LE (2002) The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling. EMBO J 21:3536–3545
Lejeune F, Ranganathan AC, Maquat LE (2004) eIF4G is required for the pioneer round of translation in mammalian cells. Nat Struct Mol Biol 11:992–1000
Chiu SY, Lejeune F, Ranganathan AC et al (2004) The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev 18:745–754
Zhang J, Sun X, Qian Y et al (1998) At least one intron is required for the nonsense-mediated decay of triosephosphate isomerase mRNA: a possible link between nuclear splicing and cytoplasmic translation. Mol Cell Biol 18:5272–5283
Coller J, Parker R (2004) Eukaryotic mRNA decapping. Annu Rev Biochem 73:861–890
Coller J, Parker R (2005) General translational repression by activators of mRNA decapping. Cell 122:875–886
Ferraiuolo MA, Basak S, Dostie J et al (2005) A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay. Cell Biol 170:913–924
Braun KA, Young ET (2014) Coupling mRNA synthesis and decay. Mol Cell Biol 34:4078–4087
Linde L, Kerem B (2008) Introducing sense into nonsense in treatments of human genetic diseases. Trends Genet 24:552–563
Geiger SK, Bar H, Ehlermann P et al (2008) Incomplete nonsense-mediated decay of mutant lamin A/C mRNA provokes dilated cardiomyopathy and ventricular tachycardia. J Mol Med 86:281–289
Gong Q, Zhang L, Vincent GM et al (2007) Nonsense mutations in hERG cause a decrease in mutant mRNA transcripts by nonsense-mediated mRNA decay in human long-QT syndrome. Circulation 116:17–24
Zarraga IG, Zhang L, Stump MR et al (2011) Nonsense-mediated mRNA decay caused by a frameshift mutation in a large kindred of type 2 long QT syndrome. Heart Rhythm 8:1200–1206
Vignier N, Schlossarek S, Fraysse B et al (2009) Nonsense-mediated mRNA decay and ubiquitin-proteasome system regulate cMyBP-C mutant levels in cardiomyopathic mice. Circ Res 105:239–248
Suzuki S, Nakao A, Sarhat AR et al (2014) A case of pancreatic agenesis and congenital heart defects with a novel GATA6 nonsense mutation: evidence of haploinsufficiency due to nonsense-mediated mRNA decay. Am J Med Genet A 2014(164A):476–479
Mani A, Radhakrishnan J, Farhi A et al (2005) Syndromic patent ductus arteriosus: evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder. Proc Natl Acad Sci U S A 102:2975–2979
Chen Z, Eggerman TL, Patterson AP (2007) ApoB mRNA editing is mediated by a coordinated modulation of multiple apoB mRNA editing enzyme components. Am J Physiol Gastrointest Liver Physiol 292:G53–G65
Wedekind JE, Dance GS, Sowden MP et al (2003) Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business. Trends Genet 19:207–216
Galeano F, Tomaselli S, Locatelli F et al (2012) A-to-I RNA editing: the “ADAR” side of human cancer. Semin Cell Dev Biol 23:244–250
Anant S, Henderson J, Mukhopadhyay D et al (2001) Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. J Biol Chem 276:47338–47351
Blanc V, Davidson NO (2003) C-to-U RNA editing: mechanisms leading to genetic diversity. J Biol Chem 278:1395–1398
Zhang H (2010) The inhibitory effect of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members on the activity of cellular microRNAs. Prog Mol Subcell Biol 50:71–83
Dasgupta T, Ladd AN (2012) The importance of CELF control: molecular and biological roles of the CUG-BP, Elav-like family of RNA-binding proteins. Wiley Interdiscip Rev RNA 3:104–121
Ohman M (2007) A-to-I editing challenger or ally to the microRNA process. Biochimie 89:1171–1176
Nishikura K (2010) Functions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem 79:321–349
Franca R, Spadari S, Maga G (2006) APOBEC deaminases as cellular antiviral factors: a novel natural host defense mechanism. Med Sci Monit 12:RA92–RA98
Vieira VC, Soares MA (2013) The role of cytidine deaminases on innate immune responses against human viral infections. Biomed Res Int 2013:683095
van den Hoogen BG, van Boheemen S, de Rijck J et al (2014) Excessive production and extreme editing of human metapneumovirus defective interfering RNA is associated with type I IFN induction. J Gen Virol 95:1625–1633
Sarvestani ST, Tate MD, Moffat JM et al (2014) Inosine-mediated modulation of RNA sensing by Toll-like receptor 7 (TLR7) and TLR8. J Virol 88:799–810
Clerzius G, Shaw E, Daher A et al (2013) The PKR activator, PACT, becomes a PKR inhibitor during HIV-1 replication. Retrovirology 10:96
Avesson L, Barry G (2014) The emerging role of RNA and DNA editing in cancer. Biochim Biophys Acta 1845:308–316
Dominissini D, Moshitch-Moshkovitz S, Amariglio N et al (2011) Adenosine-to-inosine RNA editing meets cancer. Carcinogenesis 2011(32):1569–1577
Li D, Bachinski L, Roberts R (2001) Genomic organization and isoform-specific tissue expression of human NAPOR (CUGBP2) as a candidate gene for familial arrhythmogenic right ventricular dysplasia. Genomics 74:396–401
Lichtner P, Attié-Bitach T, Schuffenhauer S et al (2002) Expression and mutation analysis of Brunol3, a candidate gene for heart and thymus developmental defects associated with partial monosomy 10p. J Mol Med 80:431–442
Wang Z, Burge CB (2008) Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 14:802–813
Burge CB, Tuschl T, Sharp PA (1999) Splicing of precursors to mRNAs by the spliceosomes. In: Gesteland RF et al (eds) The RNA world. Cold Spring Harbor Press, Cold Spring Harbor, pp 525–560
Hastings ML, Krainer AR (2001) Pre-mRNA splicing in the new millennium. Curr Opin Cell Biol 13:302–309
Black DL (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem 72:291–336
Nissim-Rafinia M, Kerem B (2002) Splicing regulation as a potential genetic modifier. Trends Genet 18:123–127
Han J, Xiong J, Wang D et al (2011) Pre-mRNA splicing: where and when in the nucleus. Trends Cell Biol 21:336–343
Lara-Pezzi E, Gómez-Salinero J, Gatto A, García-Pavía P (2013) The alternative heart: impact of alternative splicing in heart disease. J Cardiovasc Transl Res 6:945–955
Ria M, Eriksson P, Boquist S et al (2006) Human genetic evidence that OX40 is implicated in myocardial infarction. Biochem Biophys Res Commun 339:1001–1006
Maatz H, Jens M, Liss M et al (2014) RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing. J Clin Invest 124:3419–3430
Brauch KM, Karst ML, Herron KJ et al (2009) Mutations in ribonucleic acid binding protein gene cause familial dilated cardiomyopathy. J Am Coll Cardiol 54:930–941
Rimessi P, Fabris M, Bovolenta M et al (2010) Antisense modulation of both exonic and intronic splicing motifs induces skipping of a DMD pseudo-exon responsible for x-linked dilated cardiomyopathy. Hum Gene Ther 21:1137–1146
Ruiz-Lozano P, Doevendans P, Brown A et al (1997) Developmental expression of the murine spliceosome-associated protein mSAP49. Dev Dyn 208:482–490
Xu X, Yang D, Ding JH et al (2005) ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle. Cell 120:59–72
Feng Y, Valley MT, Lazar J et al (2009) SRp38 regulates alternative splicing and is required for Ca(2+) handling in the embryonic heart. Dev Cell 16:528–538
Dally S, Corvazier E, Bredoux R et al (2010) Multiple and diverse coexpression, location, and regulation of additional SERCA2 and SERCA3 isoforms in nonfailing and failing human heart. J Mol Cell Cardiol 48:633–644
Schroeter A, Walzik S, Blechschmidt S et al (2010) Structure and function of splice variants of the cardiac voltage-gated sodium channel Na(v)1.5. J Mol Cell Cardiol 49:16–24
Valadkhan S, Jaladat Y (2010) The spliceosomal proteome: at the heart of the largest cellular ribonucleoprotein machine. Proteomics 10:4128–4141
Zhang SS, Shaw RM (2013) Multilayered regulation of cardiac ion channels. Biochim Biophys Acta 1833:876–885
Kjellqvist S, Maleki S, Olsson T et al (2013) A combined proteomic and transcriptomic approach shows diverging molecular mechanisms in thoracic aortic aneurysm development in patients with tricuspid- and bicuspid aortic valve. Mol Cell Proteomics 12:407–425
Sheng JJ, Jin JP (2014) Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review. Front Physiol 5:165
Biesiadecki BJ, Elder BD, Yu ZB, Jin JP (2002) Cardiac troponin T variants produced by aberrant splicing of multiple exons in animals with high instances of dilated cardiomyopathy. J Biol Chem 277:50275–50285
Biesiadecki BJ, Jin JP (2002) Exon skipping in cardiac troponin T of turkeys with inherited dilated cardiomyopathy. J Biol Chem 277:18459–18468
Wei B, Gao J, Huang XP, Jin JP (2010) Mutual rescues between two dominant negative mutations in cardiac troponin I and cardiac troponin T. J Biol Chem 285:27806–27816
Hoogaars WM, Barnett P, Rodriguez M et al (2008) TBX3 and its splice variant TBX3 + exon 2a are functionally similar. Pigment Cell Melanoma Res 21:379–387
Georges R, Nemer G, Morin M et al (2008) Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation. Mol Cell Biol 28:4052–4067
DeBenedittis P, Jiao K (2011) Alternative splicing of T-box transcription factor genes. Biochem Biophys Res Commun 412:513–517
Ueyama T, Kasahara H, Ishiwata T et al (2003) Myocardin expression is regulated by Nkx2.5, and its function is required for cardiomyogenesis. Mol Cell Biol 23:9222–9232
Iida K, Hidaka K, Takeuchi M et al (1999) Expression of MEF2 genes during human cardiac development. Tohoku J Exp Med 187:15–23
Zhu B, Gulick T (2004) Phosphorylation and alternative pre-mRNA splicing converge to regulate myocyte enhancer factor 2C activity. Mol Cell Biol 24:8264–8275
Schweickert A, Campione M, Steinbeisser H et al (2000) Pitx2 isoforms: involvement of Pitx2c but not Pitx2a or Pitx2b in vertebrate left-right asymmetry. Mech Dev 90:41–51
Yu X, St Amand TR, Wang S et al (2001) Differential expression and functional analysis of Pitx2 isoforms in regulation of heart looping in the chick. Development 128:1005–1013
Lamba P, Hjalt TA, Bernard DJ (2008) Novel forms of Paired-like homeodomain transcription factor 2 (PITX2): generation by alternative translation initiation and mRNA splicing. BMC Mol Biol 9:31
Mazaud Guittot S, Bouchard MF, Robert-Grenon JP et al (2009) Conserved usage of alternative 5′ untranslated exons of the GATA4 gene. PLoS One 4(12):e8454
Yehya A, Souki R, Bitar F et al (2006) Differential duplication of an intronic region in the NFATC1 gene in patients with congenital heart disease. Genome 49:1092–1098
Bedard JE, Haaning AM, Ware SM (2011) Identification of a novel ZIC3 isoform and mutation screening in patients with heterotaxy and congenital heart disease. PLoS One 6(8):e23755
McCright B, Gao X, Shen L et al (2001) Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development 128:491–502
Ricci M, Xu Y, Hammond HL et al (2012) Myocardial alternative RNA splicing and gene expression profiling in early stage hypoplastic left heart syndrome. PLoS One 7(1):e29784
Paloschi V, Kurtovic S, Folkersen L et al (2011) Impaired splicing of fibronectin is associated with thoracic aortic aneurysm formation in patients with bicuspid aortic valve. Arterioscler Thromb Vasc Biol 31:691–697
Murphy LL, Moon-Grady AJ, Cuneo BF et al (2012) Developmentally regulated SCN5A splice variant potentiates dysfunction of a novel mutation associated with severe fetal arrhythmia. Heart Rhythm 9:590–597
Huang H, Zhang B, Hartenstein PA et al (2005) NXT2 is required for embryonic heart development in zebrafish. BMC Dev Biol 5:7
Ver Heyen M, Heymans S, Antoons G et al (2001) Replacement of the muscle-specific sarcoplasmic reticulum Ca(2+)-ATPase isoform SERCA2a by the nonmuscle SERCA2b homologue causes mild concentric hypertrophy and impairs contraction-relaxation of the heart. Circ Res 89:838–846
Buyon JP, Tseng CE, Di Donato F et al (1997) Cardiac expression of 52beta, an alternative transcript of the congenital heart block-associated 52-kd SS-A/Ro autoantigen, is maximal during fetal development. Arthritis Rheum 40:655–660
Schonrock N, Harvey RP, Mattick JS (2012) Long noncoding RNAs in cardiac development and pathophysiology. Circ Res 111:1349–1362
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Bauersachs J, Thum T (2011) Biogenesis and regulation of cardiovascular microRNAs. Circ Res 109(3):334–347
Espinoza-Lewis RA, Wang DZ (2012) MicroRNAs in heart development. Curr Top Dev Biol 100:279–317
Chen J, Wang DZ (2012) microRNAs in cardiovascular development. J Mol Cell Cardiol 52:949–957
Bonet F, Hernandez-Torres F, Franco D (2014) Towards the therapeutic usage of microRNAs in cardiac disease and regeneration. Exp Clin Cardiol 20:720–756
Chinchilla A, Lozano E, Daimi H et al (2011) MicroRNA profiling during mouse ventricular maturation: a role for miR-27 modulating Mef2c expression. Cardiovasc Res 89:98–108
Vacchi-Suzzi C, Hahne F, Scheubel P et al (2013) Heart structure-specific transcriptomic atlas reveals conserved microRNA-mRNA interactions. PLoS One 8:e52442
Porrello ER, Mahmoud AI, Simpson E et al (2013) Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc Natl Acad Sci U S A 110:187–192
Hsu J, Hanna P, Van Wagoner DR et al (2012) Whole genome expression differences in human left and right atria ascertained by RNA sequencing. Circ Cardiovasc Genet 5:327–335
Boon RA, Iekushi K, Lechner S et al (2013) MicroRNA-34a regulates cardiac ageing and function. Nature 495:107–110
Dimmeler S, Nicotera P (2013) MicroRNAs in age-related diseases. EMBO Mol Med 5(2):180–190
van Rooij E, Sutherland LB, Liu N et al (2006) A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A 103:18255–18260
Care A, Catalucci D, Felicetti F et al (2007) MicroRNA-133 controls cardiac hypertrophy. Nat Med 13:613–618
Sayed D, Hong C, Chen IY et al (2007) MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 100:416–424
Fernandes T, Hashimoto NY, Magalhães FC et al (2011) Aerobic exercise training-induced left ventricular hypertrophy involves regulatory MicroRNAs, decreased angiotensin-converting enzyme-angiotensin ii, and synergistic regulation of angiotensin-converting enzyme 2-angiotensin. Hypertension 58:182–189
Yang KC, Ku YC, Lovett M, Nerbonne JM (2012) Combined deep microRNA and mRNA sequencing identifies protective transcriptomal signature of enhanced PI3Kα signaling in cardiac hypertrophy. J Mol Cell Cardiol 53:101–112
Reddy S, Zhao M, Hu DQ et al (2012) Dynamic microRNA expression during the transition from right ventricular hypertrophy to failure. Physiol Genomics 44:562–575
van Rooij E, Sutherland LB, Thatcher JE et al (2008) Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A 105:13027–13032
Drake JI, Bogaard HJ, Mizuno S et al (2011) Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol 45(6):1239–1247
Yang KC, Yamada KA, Patel AY et al (2014) Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support. Circulation 129:1009–1021
Lu Y, Zhang Y, Wang N et al (2010) MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation. Circulation 122:2378–2387
Xiao J, Liang D, Zhang Y et al (2011) MicroRNA expression signature in atrial fibrillation with mitral stenosis. Physiol Genomics 43:655–664
Cooley N, Cowley MJ, Lin RC et al (2012) Influence of atrial fibrillation on microRNA expression profiles in left and right atria from patients with valvular heart disease. Physiol Genomics 44:211–219
Liu Z, Zhou C, Liu Y et al (2012) The expression levels of plasma microRNAs in atrial fibrillation patients. PLoS One 7(9):e44906
Nishi H, Sakaguchi T, Miyagawa S et al (2013) Impact of microRNA expression in human atrial tissue in patients with atrial fibrillation undergoing cardiac surgery. PLoS One 8:e73397
Liu G, Huang Y, Lu X et al (2010) Identification and characteristics of microRNAs with altered expression patterns in a rat model of abdominal aortic aneurysms. Tohoku J Exp Med 222:187–193
Zhao Y, Ransom JF, Li A et al (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129:303–317
Saxena A, Tabin CJ (2010) miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation. Proc Natl Acad Sci U S A 107:87–91
Singh MK, Lu MM, Massera D et al (2011) MicroRNA-processing enzyme Dicer is required in epicardium for coronary vasculature development. J Biol Chem 286:41036–41045
Fish JE, Santoro MM, Morton SU et al (2008) miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15:272–284
Xing HJ, Li YJ, Ma QM et al (2013) Identification of microRNAs present in congenital heart disease associated copy number variants. Eur Rev Med Pharmacol Sci 17(15):2114–2120
Li D, Ji L, Liu L et al (2014) Characterization of circulating microRNA expression in patients with a ventricular septal defect. PLoS One 9:e106318
Zhang J, Chang JJ, Xu F et al (2013) MicroRNA deregulation in right ventricular outflow tract myocardium in nonsyndromic tetralogy of fallot. Can J Cardiol 29:1695–1703
Lai CT, Ng EK, Chow PC et al (2013) Circulating microRNA expression profile and systemic right ventricular function in adults after atrial switch operation for complete transposition of the great arteries. BMC Cardiovasc Disord 13:73
Yu ZB, Han SP, Bai YF et al (2012) microRNA expression profiling in fetal single ventricle malformation identified by deep sequencing. Int J Mol Med 29:53–60
Nigam V, Sievers HH, Jensen BC et al (2010) Altered microRNAs in bicuspid aortic valve: a comparison between stenotic and insufficient valves. J Heart Valve Dis 19:459–465
de la Morena MT, Eitson JL, Dozmorov IM et al (2013) Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome. Clin Immunol 147:11–22
Zhu S, Cao L, Zhu J et al (2013) Identification of maternal serum microRNAs as novel non-invasive biomarkers for prenatal detection of fetal congenital heart defects. Clin Chim Acta 424:66–72
Yu Z, Han S, Hu P et al (2011) Potential role of maternal serum microRNAs as a biomarker for fetal congenital heart defects. Med Hypotheses 76:424–426
Omran A, Elimam D, Webster KA et al (2013) MicroRNAs: a new piece in the paediatric cardiovascular disease puzzle. Cardiol Young 23:642–655
Ounzain S, Pezzuto I, Micheletti R et al (2014) Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease. J Mol Cell Cardiol 76:55–70
Scheuermann JC, Boyer LA (2013) Getting to the heart of the matter: long non-coding RNAs in cardiac development and disease. EMBO J 32:1805–1816
Caley DP, Pink RC, Trujillano D et al (2010) Long noncoding RNAs, chromatin, and development. ScientificWorldJournal 10:90–102
Zhu S, Hu X, Han S et al (2014) Differential expression profile of long non-coding RNAs during differentiation of cardiomyocytes. Int J Med Sci 11:500–507
Zhu JG, Shen YH, Liu HL et al (2014) Long noncoding RNAs expression profile of the developing mouse heart. J Cell Biochem 115:910–918
Kaushik K, Leonard VE, Kv S et al (2013) Dynamic expression of long non-coding RNAs (lncRNAs) in adult zebrafish. PLoS One 8:e83616
Zhang L, Hamad EA, Vausort M et al (2015) Identification of candidate long noncoding RNAs associated with left ventricular hypertrophy. Clin Transl Sci 8:100–106
Ounzain S, Micheletti R, Beckmann T et al (2015) Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs. Eur Heart J 36:353–368
Liu Y, Li G, Lu H et al (2014) Expression profiling and ontology analysis of long noncoding RNAs in post-ischemic heart and their implied roles in ischemia/reperfusion injury. Gene 543:15–21
Liu J, Wang DZ (2014) An epigenetic “LINK(RNA)” to pathological cardiac hypertrophy. Cell Metab 20:555–557
Han P, Li W, Lin CH et al (2014) A long noncoding RNA protects the heart from pathological hypertrophy. Nature 514:102–106
Song G, Shen Y, Zhu J et al (2013) Integrated analysis of dysregulated lncRNA expression in fetal cardiac tissues with ventricular septal defect. PLoS One 8:e77492
O’Brien JE Jr, Kibiryeva N, Zhou XG et al (2012) Noncoding RNA expression in myocardium from infants with tetralogy of Fallot. Circ Cardiovasc Genet 5:279–286
Grote P, Wittler L, Hendrix D et al (2013) The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell 24:206–214
Klattenhoff CA, Scheuermann JC, Surface LE et al (2013) Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell 152:570–583
Chen LL, Yang L (2015) Regulation of circRNA biogenesis. RNA Biol 12:381–388
Lasda E, Parker R (2014) Circular RNAs: diversity of form and function. RNA 20:1829–1842
Matkovich SJ, Edwards JR, Grossenheider TC et al (2014) Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs. Proc Natl Acad Sci U S A 111(33):12264–12269
Kalsotra A, Wang K, Li PF et al (2010) MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development. Genes Dev 24:653–658
Xu J, Hu Z, Xu Z et al (2009) Functional variant in microRNA-196a2 contributes to the susceptibility of congenital heart disease in a Chinese population. Hum Mutat 30:1231–1236
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer-Verlag Wien
About this chapter
Cite this chapter
Aranega, A.E., Franco, D. (2016). Post-transcriptional Regulation by Proteins and Non-coding RNAs. In: Rickert-Sperling, S., Kelly, R., Driscoll, D. (eds) Congenital Heart Diseases: The Broken Heart. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1883-2_13
Download citation
DOI: https://doi.org/10.1007/978-3-7091-1883-2_13
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-1882-5
Online ISBN: 978-3-7091-1883-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)