miR-1/133a Clusters Cooperatively Specify the Cardiomyogenic Lineage by Adjustment of Myocardin Levels during Embryonic Heart Development

English version České info

miRNAs are small RNAs directing many developmental processes by posttranscriptional regulation of protein-coding genes. We uncovered a new role for miR-1-1/133a-2 and miR-1-2/133a-1 clusters in the specification of embryonic cardiomyocytes allowing transition from an immature state characterized by expression of smooth muscle (SM) genes to a more mature fetal phenotype. Concomitant knockout of miR-1-1/133a-2 and miR-1-2/133a-1 released suppression of the transcriptional co-activator myocardin, a major regulator of SM gene expression, but not of its binding partner SRF. Overexpression of myocardin in the embryonic heart essentially recapitulated the miR-1/133a mutant phenotype at the molecular level, arresting embryonic cardiomyocytes in an immature state. Interestingly, the majority of postulated miR-1/133a targets was not altered in double mutant mice, indicating that the ability of miR-1/133a to suppress target molecules strongly depends on the cellular context. Finally, we show that myocardin positively regulates expression of miR-1/133a, thus constituting a negative feedback loop that is essential for early cardiac development.

Vyšlo v časopise: miR-1/133a Clusters Cooperatively Specify the Cardiomyogenic Lineage by Adjustment of Myocardin Levels during Embryonic Heart Development. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003793
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003793

Souhrn

Zdroje

1. MoormanAF, ChristoffelsVM (2003) Cardiac chamber formation: development, genes, and evolution. Physiol Rev 83: 1223–1267.

2. RuzickaDL, SchwartzRJ (1988) Sequential activation of alpha-actin genes during avian cardiogenesis: vascular smooth muscle alpha-actin gene transcripts mark the onset of cardiomyocyte differentiation. J Cell Biol 107: 2575–2586.

3. LiL, MianoJM, CserjesiP, OlsonEN (1996) SM22 alpha, a marker of adult smooth muscle, is expressed in multiple myogenic lineages during embryogenesis. Circ Res 78: 188–195.

4. BoettgerT, BeetzN, KostinS, SchneiderJ, KrugerM, et al. (2009) Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest 119: 2634–2647.

5. HuangJ, ElickerJ, BowensN, LiuX, ChengL, et al. (2012) Myocardin regulates BMP-10 expression and is required for heart development. J Clin Invest 122: 3678–3691.

6. BoettgerT, BraunT (2012) A new level of complexity: the role of microRNAs in cardiovascular development. Circ Res 110: 1000–1013.

7. WangC, CaoD, WangQ, WangDZ (2011) Synergistic activation of cardiac genes by myocardin and Tbx5. PLoS One 6: e24242.

8. van RooijE, QuiatD, JohnsonBA, SutherlandLB, QiX, et al. (2009) A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell 17: 662–673.

9. CallisTE, PandyaK, SeokHY, TangRH, TatsuguchiM, et al. (2009) MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 119: 2772–2786.

10. CreemersEE, SutherlandLB, OhJ, BarbosaAC, OlsonEN (2006) Coactivation of MEF2 by the SAP domain proteins myocardin and MASTR. Mol Cell 23: 83–96.

11. SweetmanD, RathjenT, JeffersonM, WheelerG, SmithTG, et al. (2006) FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos. Dev Dyn 235: 2185–2191.

12. ChenJF, MandelEM, ThomsonJM, WuQ, CallisTE, et al. (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38: 228–233.

13. LiuN, WilliamsAH, KimY, McAnallyJ, BezprozvannayaS, et al. (2007) An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133. Proc Natl Acad Sci U S A 104: 20844–20849.

14. ZhaoY, SamalE, SrivastavaD (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436: 214–220.

15. LiuN, BezprozvannayaS, WilliamsAH, QiX, RichardsonJA, et al. (2008) microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev 22: 3242–3254.

16. ZhaoY, RansomJF, LiA, VedanthamV, von DrehleM, et al. (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129: 303–317.

17. IkedaS, HeA, KongSW, LuJ, BejarR, et al. (2009) MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Mol Cell Biol 29: 2193–2204.

18. ChenH, ShiS, AcostaL, LiW, LuJ, et al. (2004) BMP-10 is essential for maintaining cardiac growth during murine cardiogenesis. Development 131: 2219–2231.

19. GassmannM, CasagrandaF, OrioliD, SimonH, LaiC, et al. (1995) Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature 378: 390–394.

20. ChenYH, IshiiM, SucovHM, MaxsonREJr (2008) Msx1 and Msx2 are required for endothelial-mesenchymal transformation of the atrioventricular cushions and patterning of the atrioventricular myocardium. BMC Dev Biol 8: 75.

21. GuoC, SunY, ZhouB, AdamRM, LiX, et al. (2011) A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. J Clin Invest 121: 1585–1595.

22. ImamuraM, LongX, NandaV, MianoJM (2010) Expression and functional activity of four myocardin isoforms. Gene 464: 1–10.

23. LongX, TharpDL, GeorgerMA, SlivanoOJ, LeeMY, et al. (2009) The smooth muscle cell-restricted KCNMB1 ion channel subunit is a direct transcriptional target of serum response factor and myocardin. J Biol Chem 284: 33671–33682.

24. PipesGC, CreemersEE, OlsonEN (2006) The myocardin family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesis. Genes Dev 20: 1545–1556.

25. HuangJ, Min LuM, ChengL, YuanLJ, ZhuX, et al. (2009) Myocardin is required for cardiomyocyte survival and maintenance of heart function. Proc Natl Acad Sci U S A 106: 18734–18739.

26. XingW, ZhangTC, CaoD, WangZ, AntosCL, et al. (2006) Myocardin induces cardiomyocyte hypertrophy. Circ Res 98: 1089–1097.

27. WangZ, WangDZ, PipesGC, OlsonEN (2003) Myocardin is a master regulator of smooth muscle gene expression. Proc Natl Acad Sci U S A 100: 7129–7134.

28. LongX, BellRD, GerthofferWT, ZlokovicBV, MianoJM (2008) Myocardin is sufficient for a smooth muscle-like contractile phenotype. Arterioscler Thromb Vasc Biol 28: 1505–1510.

29. BoogerdCJ, MoormanAF, BarnettP (2010) Expression of muscle segment homeobox genes in the developing myocardium. Anat Rec (Hoboken) 293: 998–1001.

30. ConsortiumEP, DunhamI, KundajeA, AldredSF, CollinsPJ, et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74.

31. MeunierJ, LemoineF, SoumillonM, LiechtiA, WeierM, et al. (2013) Birth and expression evolution of mammalian microRNA genes. Genome Res 23: 34–45.

32. BerndtJD, AoyagiA, YangP, AnastasJN, TangL, et al. (2011) Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/beta-catenin signaling. J Cell Biol 194: 737–750.

33. KangK, LeeD, HongS, ParkSG, SongMR (2012) The E3 ligase mindbomb-1 (Mib1) modulates Delta-Notch signaling to control neurogenesis and gliogenesis in the developing spinal cord. J Biol Chem 288: 2580–2592.

34. LiS, WangDZ, WangZ, RichardsonJA, OlsonEN (2003) The serum response factor coactivator myocardin is required for vascular smooth muscle development. Proc Natl Acad Sci U S A 100: 9366–9370.

35. HoofnagleMH, NepplRL, BerzinEL, Teg PipesGC, OlsonEN, et al. (2011) Myocardin is differentially required for the development of smooth muscle cells and cardiomyocytes. Am J Physiol Heart Circ Physiol 300: H1707–1721.

36. TorradoM, LopezE, CentenoA, MedranoC, Castro-BeirasA, et al. (2003) Myocardin mRNA is augmented in the failing myocardium: expression profiling in the porcine model and human dilated cardiomyopathy. J Mol Med (Berl) 81: 566–577.

37. LarsonAC, WhiteRD, LaubG, McVeighER, LiD, et al. (2004) Self-gated cardiac cine MRI. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine/Society of Magnetic Resonance in Medicine 51: 93–102.