Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD.
Yu X1, Zhang Y1, Li T2, Ma Z3, Jia H1, Chen Q1, Zhao Y1, Zhai L1, Zhong R1, Li C1, Zou X1, Meng J1, Chen AK3, Puri PL4,5, Chen M1, Zhu D1.
Nat Commun. 2017 Jan 16;8:14016.
PMID: 28091529 PMCID: PMC5241866 DOI: 10.1038/ncomms14016
Abstract
Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes. Here we report on functional identification and characterization of a novel long intergenic non-coding RNA with MyoD-regulated and skeletal muscle-restricted expression that promotes the activation of the myogenic program, and is therefore termed Linc-RAM (Linc-RNA Activator of Myogenesis). Linc-RAM is transcribed from an intergenic region of myogenic cells and its expression is upregulated during myogenesis. Notably, in vivo functional studies show that Linc-RAM knockout mice display impaired muscle regeneration due to the differentiation defect of satellite cells. Mechanistically, Linc-RAM regulates expression of myogenic genes by directly binding MyoD, which in turn promotes the assembly of the MyoD-Baf60c-Brg1 complex on the regulatory elements of target genes. Collectively, our findings reveal the functional role and molecular mechanism of a lineage-specific Linc-RAM as a regulatory lncRNA required for tissues-specific chromatin remodelling and gene expression.