Uncoupling of Expression of an Intronic MicroRNA and Its Myosin Host Gene by Exon Skipping

被引:125
作者
Bell, Matthew L. [1 ]
Buvoli, Massimo [1 ]
Leinwand, Leslie A. [1 ]
机构
[1] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA
关键词
SKELETAL-MUSCLE; FATE DETERMINATION; FEEDBACK LOOP; IN-VITRO; SOX6; DIFFERENTIATION; PROTEINS; CELLS; HYPERTROPHY; HEART;
D O I
10.1128/MCB.01370-09
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The ancient MYH7b gene, expressed in striated muscle and brain, encodes a sarcomeric myosin and the intronic microRNA miR-499. We find that skipping of an exon introduces a premature termination codon in the transcript that downregulates MYH7b protein production without affecting microRNA expression. Among other genes, endogenous miR-499 targets the 3' untranslated region of the transcription factor Sox6, which in turn acts as a repressor of MYH7b transcriptional activity. Thus, concerted transcription and alternative splicing uncouple the level of expression of MYH7b and miR-499 when their coexpression is not required.
引用
收藏
页码:1937 / 1945
页数:9
相关论文
共 45 条
[1]
Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse [J].
Allen, DL ;
Harrison, BC ;
Maass, AH ;
Bell, ML ;
Byrnes, WC ;
Leinwand, LA .
JOURNAL OF APPLIED PHYSIOLOGY, 2001, 90 (05) :1900-1908
[2]
Dose-dependent blockade to cardiomyocyte hypertrophy by histone deacetylase inhibitors [J].
Antos, CL ;
McKinsey, TA ;
Dreitz, M ;
Hollingsworth, LM ;
Zhang, CL ;
Schreiber, K ;
Rindt, H ;
Gorczynski, RJ ;
Olson, EN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (31) :28930-28937
[3]
A systematic analysis of intronic sequences downstream of 5′ splice sites reveals a widespread role for U-rich motifs and TIA1/TIAL1 proteins in alternative splicing regulation [J].
Aznarez, Isabel ;
Barash, Yoseph ;
Shai, Ofer ;
He, David ;
Zielenski, Julian ;
Tsui, Lap-Chee ;
Parkinson, John ;
Frey, Brendan J. ;
Rommens, Johanna M. ;
Blencowe, Benjamin J. .
GENOME RESEARCH, 2008, 18 (08) :1247-1258
[4]
Sequence conservation, relative isoform frequencies, and nonsense-mediated decay in evolutionarily conserved alternative splicing [J].
Baek, D ;
Green, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (36) :12813-12818
[5]
Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes [J].
Baskerville, S ;
Bartel, DP .
RNA, 2005, 11 (03) :241-247
[6]
MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice [J].
Callis, Thomas E. ;
Pandya, Kumar ;
Seok, Hee Young ;
Tang, Ru-Hang ;
Tatsuguchi, Mariko ;
Huang, Zhan-Peng ;
Chen, Jian-Fu ;
Deng, Zhongliang ;
Gunn, Bronwyn ;
Shumate, Janelle ;
Willis, Monte S. ;
Selzman, Craig H. ;
Wang, Da-Zhi .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (09) :2772-2786
[7]
A REGULATORY MECHANISM THAT DETECTS PREMATURE NONSENSE CODONS IN T-CELL RECEPTOR TRANSCRIPTS IN-VIVO IS REVERSED BY PROTEIN-SYNTHESIS INHIBITORS IN-VITRO [J].
CARTER, MS ;
DOSKOW, J ;
MORRIS, P ;
LI, SL ;
NHIM, RP ;
SANDSTEDT, S ;
WILKINSON, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (48) :28995-29003
[8]
Identifying pattern-defined regulatory islands in mammalian genomes [J].
Cheung, Tom H. ;
Barthel, Kristen K. B. ;
Kwan, Yin Lam ;
Liu, Xuedong .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (24) :10116-10121
[9]
Sox6 regulation of cardiac myocyte development [J].
Cohen-Barak, O ;
Yi, ZH ;
Hagiwara, N ;
Monzen, K ;
Komuro, I ;
Brilliant, MH .
NUCLEIC ACIDS RESEARCH, 2003, 31 (20) :5941-5948
[10]
THE SRY-RELATED HMG BOX-CONTAINING GENE SOX6 IS EXPRESSED IN THE ADULT TESTIS AND DEVELOPING NERVOUS-SYSTEM OF THE MOUSE [J].
CONNOR, F ;
WRIGHT, E ;
DENNY, P ;
KOOPMAN, P ;
ASHWORTH, A .
NUCLEIC ACIDS RESEARCH, 1995, 23 (17) :3365-3372