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

• DOI: 10.1016/j.devcel.2015.05.009
• Publication Date: 2015-07-04T20:44:27Z
• Authors: Chenguang Gong; Zhizhong Li; Krishnan Ramanujan; Ieuan Clay; Yunyu Zhang; Sophie Lemire-Bra...; David J. Glass
• Keywords: Mice, Knockout; 0303 health sciences; HMGA2 Protein; RNA-Binding Proteins; Cell Differentiation; Muscle Development; Cell Line; Mice, Inbred C57BL; Myoblasts; Proto-Oncogene Proteins c-myc; Mice; 03 medical and health sciences; Animals; RNA Interference; RNA, Long Noncoding; RNA, Small Interfering; Muscle, Skeletal; Developmental Biology; Cell Proliferation; Monomeric GTP-Binding Proteins; MyoD Protein

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.