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 （In...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 （IncRNAs） play key roles in regulating cell fate decision and function in various tissues. However, the role of IncRNAs in the regulation of myogenesis remains poorly understood. In this study, we identifed a novel muscle-enriched IncRNA 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 differ-entiation. 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 Filipl in a cis-manner. Similar to MyoUnc, knockdown of FiUpl inhi-bits 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. Actal 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 IncRNA that controls key regulatory networks of myogenesis.展开更多
Dear Editor,Next-generation sequencing revealed that the majority of the human genome is transcribed but has no coding function.It is estimated that.30000 long noncoding RNAs(lncRNAs)are expressed in humans,but their ...Dear Editor,Next-generation sequencing revealed that the majority of the human genome is transcribed but has no coding function.It is estimated that.30000 long noncoding RNAs(lncRNAs)are expressed in humans,but their functions are largely unknown(Suckau et al.,2009;Rinn and Chang,2012;Poller et al.,2013).Consideration of noncoding genomic elements in pathogenetic studies is warranted and enabled by technological advances allowing comprehensive transcriptome mapping of protein-coding genes as well as small and long ncRNAs.展开更多
文摘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 （IncRNAs） play key roles in regulating cell fate decision and function in various tissues. However, the role of IncRNAs in the regulation of myogenesis remains poorly understood. In this study, we identifed a novel muscle-enriched IncRNA 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 differ-entiation. 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 Filipl in a cis-manner. Similar to MyoUnc, knockdown of FiUpl inhi-bits 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. Actal 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 IncRNA that controls key regulatory networks of myogenesis.
基金supported by Deutsche Forschungsgemeinschaft through SFB/TR 19 (grants C5 to W.P.and C.S.,Z1 to U.K.and H.-P.S.,and B3 to A.V.)by DZHK (German Center for Cardiovascular Research)through DZHK Column B Shared Expertise Project SE097+1 种基金supported by Vidi grants (016.146.363 to B.S.and 91796338 to S.H.)from the Netherlands Organization for Scientific Research,a Dekker grant (2014T105 to B.S.)and research grants (2009B025 to B.S.and 2008B011 to S.H.)from the Netherlands Heart Foundation,Research Foundation Flanders (FWO 1183211N,1167610N,G074009N to S.H.),European Union FP7-HEALTH-2010 (MEDIA to S.H./B.S.)and FP7-HEALTH-2011 (EU-Mascara to S.H.)Research in K.V.P.laboratory is funded by grants from American Cancer Society (RSG-11-174-01-RMC)and NIH/NIGMS (GM088252).
文摘Dear Editor,Next-generation sequencing revealed that the majority of the human genome is transcribed but has no coding function.It is estimated that.30000 long noncoding RNAs(lncRNAs)are expressed in humans,but their functions are largely unknown(Suckau et al.,2009;Rinn and Chang,2012;Poller et al.,2013).Consideration of noncoding genomic elements in pathogenetic studies is warranted and enabled by technological advances allowing comprehensive transcriptome mapping of protein-coding genes as well as small and long ncRNAs.
