A Long Non-coding RNA, LncMyoD, Regulates Skeletal Muscle Differentiation by Blocking IMP2-Mediated mRNA Translation

• Published in: Developmental cell 2015-07, Vol.34 (2), p.181-191
• Main Authors: Gong, Chenguang, Li, Zhizhong, Ramanujan, Krishnan, Clay, Ieuan, Zhang, Yunyu, Lemire-Brachat, Sophie, Glass, David J.
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Cell Line; Cell Proliferation - genetics; HMGA2 Protein - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Monomeric GTP-Binding Proteins - biosynthesis; Muscle Development - genetics; Muscle, Skeletal - embryology; Muscle, Skeletal - growth & development; Myoblasts - cytology; MyoD Protein - genetics; Proto-Oncogene Proteins c-myc - biosynthesis; RNA Interference; RNA, Long Noncoding - genetics; RNA, Small Interfering; RNA-Binding Proteins - genetics
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2015.05.009

Increasing evidence suggests that long non-coding RNAs (LncRNAs) represent a new class of regulators of stem cells. However, the roles of LncRNAs in stem cell maintenance and myogenesis remain largely unexamined. For this study, hundreds of intergenic LncRNAs were identified that are expressed in myoblasts and regulated during differentiation. One of these LncRNAs, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation, largely due to a failure to exit the cell cycle. LncMyoD directly binds to IGF2-mRNA-binding protein 2 (IMP2) and negatively regulates IMP2-mediated translation of proliferation genes such as N-Ras and c-Myc. While the RNA sequence of LncMyoD is not well conserved between human and mouse, its locus, gene structure, and function are preserved. The MyoD-LncMyoD-IMP2 pathway elucidates a mechanism as to how MyoD blocks proliferation to create a permissive state for differentiation. [Display omitted] •LncMyoD is directly activated by MyoD during myogenesis•LncMyoD binds to IMPs and regulates mRNA translation•Human and mouse LncMyoD are functionally conserved despite low sequence homology Long non-coding RNAs are regulators of various biological functions. Gong and Li et al. show that LncMyoD is a LncRNA target of MyoD during myogenesis and is required for myoblast differentiation by affecting IMP2-mediated mRNA translation. LncMyoD is functionally conserved between mouse and human, despite limited sequence homology.