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While a large number of lncRNAs have been identified in skeletal muscles until now, their function and underlying mechanisms in skeletal myogenesis remain largely unclear.<\/jats:p><\/jats:sec>Methods<\/jats:title>We characterized a novel functional lncRNA designated lncMGPF<\/jats:italic> (lncRNA muscle growth promoting factor) using RACE, Northern blot, fluorescence in situ<\/jats:italic> hybridization and quantitative real\u2010time PCR. Its function was determined by gene overexpression, interference, and knockout experiments in C2C12 myoblasts, myogenic progenitor cells, and an animal model. The molecular mechanism by which lncMGPF<\/jats:italic> regulates muscle differentiation was mainly examined by cotransfection experiments, luciferase reporter assay, RNA immunoprecipitation, RNA pull\u2010down, and RNA stability analyses.<\/jats:p><\/jats:sec>Results<\/jats:title>We report that lncMGPF<\/jats:italic>, which is highly expressed in muscles and positively regulated by myoblast determination factor (MyoD), promotes myogenic differentiation of muscle cells in vivo<\/jats:italic> and in vitro<\/jats:italic>. lncMGPF<\/jats:italic> knockout in mice substantially decreases growth rate, reduces muscle mass, and impairs muscle regeneration. Overexpression of lncMGPF<\/jats:italic> in muscles can rescue the muscle phenotype of knockout mice and promote muscle growth of wild\u2010type mice. Mechanistically, lncMGPF<\/jats:italic> promotes muscle differentiation by acting as a molecular sponge of miR\u2010135a\u20105p and thus increasing the expression of myocyte enhancer factor 2C (MEF2C<\/jats:italic>), as well as by enhancing human antigen R\u2010mediated messenger RNA stabilization of myogenic regulatory genes such as MyoD<\/jats:italic> and myogenin<\/jats:italic> (MyoG<\/jats:italic>). We confirm that pig lncRNA AK394747<\/jats:italic> and human lncRNA MT510647<\/jats:italic> are homologous to mouse lncMGPF<\/jats:italic>, with conserved function and mechanism during myogenesis.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our data reveal that lncMGPF<\/jats:italic> is a novel positive regulator of myogenic differentiation, muscle growth and regeneration in mice, pigs, and humans.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12623","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T08:22:10Z","timestamp":1600676530000},"page":"1723-1746","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["lncMGPF<\/i> is a novel positive regulator of muscle growth and regeneration"],"prefix":"10.1002","volume":"11","author":[{"given":"Wei","family":"Lv","sequence":"first","affiliation":[{"name":"Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural 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