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Mol Cell Biol. May 1997; 17(5): 2756–2763.
PMCID: PMC232126

The MEF2A 3' untranslated region functions as a cis-acting translational repressor.


Myocyte enhancer factor 2 (MEF2) proteins serve as important muscle transcription factors. In addition, MEF2 proteins have been shown to potentiate the activity of other cell-type-specific transcription factors found in muscle and brain tissue. While transcripts for MEF2 factors are widely expressed in a variety of cells and tissues, MEF2 proteins and binding activity are largely restricted to skeletal, smooth, and cardiac muscle and to brain. This disparity between MEF2 protein and mRNA expression suggests that translational control may play an important role in regulating MEF2 expression. In an effort to identify sequences within the MEF2A message which control translation, we isolated the mouse MEF2A 3' untranslated region (UTR) and fused it to the chloramphenicol acetyltransferase (CAT) reporter gene. Here, we show by CAT assay that the MEF2A 3' UTR dramatically inhibits CAT gene expression in vivo and that this inhibition is due to an internal region within the highly conserved 3' UTR. RNase protection analyses demonstrated that the steady-state level of CAT mRNA produced in vivo was not affected by fusion of the MEF2A 3' UTR, indicating that the inhibition of CAT activity resulted from translational repression. Furthermore, fusion of the MEF2A 3' UTR to CAT inhibited translation in vitro in rabbit reticulocyte lysates. We also show that the translational repression mediated by the 3' UTR of MEF2A is regulated during muscle cell differentiation. As muscle cells in culture differentiate, the translational inhibition caused by the MEF2A 3' UTR is relaxed. These results demonstrate that the MEF2A 3' UTR functions as a cis-acting translational repressor both in vitro and in vivo and suggest that this repression may contribute to the tissue-restricted expression and binding activity of MEF2A.

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Selected References

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  • Black BL, Lyles DS. Vesicular stomatitis virus matrix protein inhibits host cell-directed transcription of target genes in vivo. J Virol. 1992 Jul;66(7):4058–4064. [PMC free article] [PubMed]
  • Black BL, Martin JF, Olson EN. The mouse MRF4 promoter is trans-activated directly and indirectly by muscle-specific transcription factors. J Biol Chem. 1995 Feb 17;270(7):2889–2892. [PubMed]
  • Black BL, Ligon KL, Zhang Y, Olson EN. Cooperative transcriptional activation by the neurogenic basic helix-loop-helix protein MASH1 and members of the myocyte enhancer factor-2 (MEF2) family. J Biol Chem. 1996 Oct 25;271(43):26659–26663. [PubMed]
  • Breitbart RE, Liang CS, Smoot LB, Laheru DA, Mahdavi V, Nadal-Ginard B. A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage. Development. 1993 Aug;118(4):1095–1106. [PubMed]
  • Buchberger A, Ragge K, Arnold HH. The myogenin gene is activated during myocyte differentiation by pre-existing, not newly synthesized transcription factor MEF-2. J Biol Chem. 1994 Jun 24;269(25):17289–17296. [PubMed]
  • Chambers AE, Kotecha S, Towers N, Mohun TJ. Muscle-specific expression of SRF-related genes in the early embryo of Xenopus laevis. EMBO J. 1992 Dec;11(13):4981–4991. [PMC free article] [PubMed]
  • Davis S, Watson JC. In vitro activation of the interferon-induced, double-stranded RNA-dependent protein kinase PKR by RNA from the 3' untranslated regions of human alpha-tropomyosin. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):508–513. [PMC free article] [PubMed]
  • Decker CJ, Parker R. Diversity of cytoplasmic functions for the 3' untranslated region of eukaryotic transcripts. Curr Opin Cell Biol. 1995 Jun;7(3):386–392. [PubMed]
  • Dodou E, Sparrow DB, Mohun T, Treisman R. MEF2 proteins, including MEF2A, are expressed in both muscle and non-muscle cells. Nucleic Acids Res. 1995 Nov 11;23(21):4267–4274. [PMC free article] [PubMed]
  • Edmondson DG, Lyons GE, Martin JF, Olson EN. Mef2 gene expression marks the cardiac and skeletal muscle lineages during mouse embryogenesis. Development. 1994 May;120(5):1251–1263. [PubMed]
  • Gossett LA, Kelvin DJ, Sternberg EA, Olson EN. A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Mol Cell Biol. 1989 Nov;9(11):5022–5033. [PMC free article] [PubMed]
  • Kaushal S, Schneider JW, Nadal-Ginard B, Mahdavi V. Activation of the myogenic lineage by MEF2A, a factor that induces and cooperates with MyoD. Science. 1994 Nov 18;266(5188):1236–1240. [PubMed]
  • Krieg PA, Melton DA. Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs. Nucleic Acids Res. 1984 Sep 25;12(18):7057–7070. [PMC free article] [PubMed]
  • Kruys V, Huez G. Translational control of cytokine expression by 3' UA-rich sequences. Biochimie. 1994;76(9):862–866. [PubMed]
  • L'Ecuyer TJ, Tompach PC, Morris E, Fulton AB. Transdifferentiation of chicken embryonic cells into muscle cells by the 3' untranslated region of muscle tropomyosin. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7520–7524. [PMC free article] [PubMed]
  • Leifer D, Golden J, Kowall NW. Myocyte-specific enhancer binding factor 2C expression in human brain development. Neuroscience. 1994 Dec;63(4):1067–1079. [PubMed]
  • Leifer D, Krainc D, Yu YT, McDermott J, Breitbart RE, Heng J, Neve RL, Kosofsky B, Nadal-Ginard B, Lipton SA. MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1546–1550. [PMC free article] [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Lyons GE, Micales BK, Schwarz J, Martin JF, Olson EN. Expression of mef2 genes in the mouse central nervous system suggests a role in neuronal maturation. J Neurosci. 1995 Aug;15(8):5727–5738. [PubMed]
  • Mao Z, Nadal-Ginard B. Functional and physical interactions between mammalian achaete-scute homolog 1 and myocyte enhancer factor 2A. J Biol Chem. 1996 Jun 14;271(24):14371–14375. [PubMed]
  • Martin JF, Miano JM, Hustad CM, Copeland NG, Jenkins NA, Olson EN. A Mef2 gene that generates a muscle-specific isoform via alternative mRNA splicing. Mol Cell Biol. 1994 Mar;14(3):1647–1656. [PMC free article] [PubMed]
  • Martin JF, Schwarz JJ, Olson EN. Myocyte enhancer factor (MEF) 2C: a tissue-restricted member of the MEF-2 family of transcription factors. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5282–5286. [PMC free article] [PubMed]
  • McCarthy JE, Kollmus H. Cytoplasmic mRNA-protein interactions in eukaryotic gene expression. Trends Biochem Sci. 1995 May;20(5):191–197. [PubMed]
  • McDermott JC, Cardoso MC, Yu YT, Andres V, Leifer D, Krainc D, Lipton SA, Nadal-Ginard B. hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors. Mol Cell Biol. 1993 Apr;13(4):2564–2577. [PMC free article] [PubMed]
  • Molkentin JD, Black BL, Martin JF, Olson EN. Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell. 1995 Dec 29;83(7):1125–1136. [PubMed]
  • Olson EN, Perry M, Schulz RA. Regulation of muscle differentiation by the MEF2 family of MADS box transcription factors. Dev Biol. 1995 Nov;172(1):2–14. [PubMed]
  • Pollock R, Treisman R. Human SRF-related proteins: DNA-binding properties and potential regulatory targets. Genes Dev. 1991 Dec;5(12A):2327–2341. [PubMed]
  • Rastinejad F, Blau HM. Genetic complementation reveals a novel regulatory role for 3' untranslated regions in growth and differentiation. Cell. 1993 Mar 26;72(6):903–917. [PubMed]
  • Rastinejad F, Conboy MJ, Rando TA, Blau HM. Tumor suppression by RNA from the 3' untranslated region of alpha-tropomyosin. Cell. 1993 Dec 17;75(6):1107–1117. [PubMed]
  • Sonenberg N. mRNA translation: influence of the 5' and 3' untranslated regions. Curr Opin Genet Dev. 1994 Apr;4(2):310–315. [PubMed]
  • Standart N, Jackson RJ. Regulation of translation by specific protein/mRNA interactions. Biochimie. 1994;76(9):867–879. [PubMed]
  • Subramanian SV, Nadal-Ginard B. Early expression of the different isoforms of the myocyte enhancer factor-2 (MEF2) protein in myogenic as well as non-myogenic cell lineages during mouse embryogenesis. Mech Dev. 1996 Jun;57(1):103–112. [PubMed]
  • Suzuki E, Guo K, Kolman M, Yu YT, Walsh K. Serum induction of MEF2/RSRF expression in vascular myocytes is mediated at the level of translation. Mol Cell Biol. 1995 Jun;15(6):3415–3423. [PMC free article] [PubMed]
  • Suzuki E, Lowry J, Sonoda G, Testa JR, Walsh K. Structures and chromosome locations of the human MEF2A gene and a pseudogene MEF2AP. Cytogenet Cell Genet. 1996;73(3):244–249. [PubMed]
  • Wahle E. 3'-end cleavage and polyadenylation of mRNA precursors. Biochim Biophys Acta. 1995 Apr 4;1261(2):183–194. [PubMed]
  • Wahle E, Keller W. The biochemistry of 3'-end cleavage and polyadenylation of messenger RNA precursors. Annu Rev Biochem. 1992;61:419–440. [PubMed]
  • Yu YT, Breitbart RE, Smoot LB, Lee Y, Mahdavi V, Nadal-Ginard B. Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. Genes Dev. 1992 Sep;6(9):1783–1798. [PubMed]

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