title: A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation.
abstract: 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.
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Gong
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Krishnan
authors.initials: K
authors.lastname: Ramanujan
authors.affiliation: Novartis Institutes for Biomedical Research, Basel 4002, Switzerland.
authors.forename: Ieuan
authors.initials: I
authors.lastname: Clay
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
authors.forename: Yunyu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Novartis Institutes for Biomedical Research, Basel 4002, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lemire-Brachat
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA. Electronic address: david.glass@novartis.com.
authors.forename: David J
authors.initials: DJ
authors.lastname: Glass
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D025743:HMGA2 Protein / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000196:embryology / Q000254:growth & development; D017570:MyoD Protein / Q000235:genetics*; D032446:Myoblasts / Q000166:cytology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D025743:HMGA2 Protein; C559768:IGF2BP2 protein, mouse; C489428:Myc protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D020559:Monomeric GTP-Binding Proteins; C586503:Nras protein, mouse