Nucleic Acids Research Advance Access originally published online on October 24, 2006
Nucleic Acids Research 2006 34(20):5863-5871; doi:10.1093/nar/gkl743
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2006, Vol. 34, No. 20 5863-5871
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
MIR-206 regulates connexin43 expression during skeletal muscle development
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Miller School of Medicine Gautier Building 303, 1011 NW 15 Street, Miami, FL 33136, USA
*To whom correspondence should be addressed. Tel: +1 305 243 6998; Fax: +1 305 243 2058; Email: rwerner{at}molbio.med.miami.edu
Received July 13, 2006. Revised September 26, 2006. Accepted September 26, 2006.
Skeletal myoblast fusion in vitro requires the expression of connexin43 (Cx43) gap junction channels. However, gap junctions are rapidly downregulated after the initiation of myoblast fusion in vitro and in vivo. In this study we show that this downregulation is accomplished by two related microRNAs, miR-206 and miR-1, that inhibit the expression of Cx43 protein during myoblast differentiation without altering Cx43 mRNA levels. Cx43 mRNA contains two binding sites for miR-206/miR-1 in its 3'-untranslated region, both of which are required for efficient downregulation. While it has been demonstrated before that miR-1 is involved in myogenesis, in this work we show that miR-206 is also upregulated during perinatal skeletal muscle development in mice in vivo and that both miR-1 and miR-206 downregulate Cx43 expression during myoblast fusion in vitro. Proper development of singly innervated muscle fibers requires muscle contraction and NMJ terminal selection and it is hypothesized that prolonged electrical coupling via gap junctions may be detrimental to this process. This work details the mechanism by which initial downregulation of Cx43 occurs during myogenesis and highlights the tight control mechanisms that are utilized for the regulation of gap junctions during differentiation and development.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Hudder and R. F. Novak miRNAs: Effectors of Environmental Influences on Gene Expression and Disease Toxicol. Sci., June 1, 2008; 103(2): 228 - 240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. F. Wong and R. L. Tellam MicroRNA-26a Targets the Histone Methyltransferase Enhancer of Zeste homolog 2 during Myogenesis J. Biol. Chem., April 11, 2008; 283(15): 9836 - 9843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Callis, Z. Deng, J.-F. Chen, and D.-Z. Wang Muscling Through the microRNA World Experimental Biology and Medicine, February 1, 2008; 233(2): 131 - 138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Greco and P. Rameshwar MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells PNAS, September 25, 2007; 104(39): 15484 - 15489. [Abstract] [Full Text] [PDF]
|
|