Journal
JOURNAL OF MOLECULAR CELL BIOLOGY
Volume 10, Issue 2, Pages 102-117Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mjy025
Keywords
long non-coding RNA; skeletal muscle; myoblasts differentiation; transcriptional regulation
Categories
Funding
- LOEWE Center for Cell and Gene Therapy (State of Hessen)
- DFG [SFB834, UC 67/2-1]
- German Center for Cardiovascular Research (DZHK)
- V.V. Cooke Foundation (Kentucky, USA)
- University of Louisville School of Medicine
- University of Louisville 21st Century University Initiative on Big Data in Medicine
- Mansbach Family
- Gheens Foundation
Ask authors/readers for more resources
Myogenesis is a complex process required for skeletal muscle formation during embryonic development and for regeneration and growth of myofibers in adults. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) play key roles in regulating cell fate decision and function in various tissues. However, the role of lncRNAs in the regulation of myogenesis remains poorly understood. In this study, we identified a novel muscle-enriched lncRNA called 'Myolinc (AK142388)', which we functionally characterized in the C2C12 myoblast cell line. Myolinc is predominately localized in the nucleus, and its levels increase upon induction of the differentiation. Knockdown of Myolinc impairs the expression of myogenic regulatory factors and formation of multi-nucleated myotubes in cultured myoblasts. Myolinc also regulates the expression of Filip1 in a cis-manner. Similar to Myolinc, knockdown of Filip1 inhibits myogenic differentiation. Furthermore, Myolinc binds to TAR DNA-binding protein 43 (TDP-43), a DNA/RNA-binding protein that regulates the expression of muscle genes (e.g. Acta1 and MyoD). Knockdown of TDP-43 inhibits myogenic differentiation. We also show that Myolinc-TDP-43 interaction is essential for the binding of TDP-43 to the promoter regions of muscle marker genes. Finally, we show that silencing of Myolinc inhibits skeletal muscle regeneration in adult mice. Altogether, our study identifies a novel lncRNA that controls key regulatory networks of myogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available