logo logo
lncRNA IGF2 AS Regulates Bovine Myogenesis through Different Pathways. Song Chengchuang,Yang Zhaoxin,Jiang Rui,Cheng Jie,Yue Binglin,Wang Jian,Sun Xiaomei,Huang Yongzhen,Lan Xianyong,Lei Chuzhao,Chen Hong Molecular therapy. Nucleic acids The role of long non-coding RNA (lncRNA) in the regulation of bovine skeletal muscle development remains poorly understood. The present study investigated the function and regulatory mechanism of a novel lncRNA, insulin-like growth factor 2 antisense transcript (IGF2 AS), in bovine myoblast proliferation and differentiation. Gain or loss of IGF2 AS was performed using an expression plasmid or small interfering RNA (siRNA), respectively. Bovine myoblasts were used to investigate the biological function and mechanisms of IGF2 AS in vitro. Results were conjointly analyzed by celluar and molecular biology experiments as well as bioinformatics. Functionally, IGF2 AS could promote proliferation and differentiation of bovine myoblasts. The preliminary mechanism suggests, on the one hand, that IGF2 AS could complement the IGF2 gene intron region and affect the stability and expression of IGF2 mRNA. On the other hand, RNA pull-down and immunoprecipitation assays demonstrated that IGF2 AS could directly bind to the interleukin enhancer binding factor 3 (ILF3) protein and maybe partly though it to regulate myogenesis. In conclusion, the novel identified lncRNA IGF2 AS promoted proliferation and differentiation of bovine myoblasts through various pathways. 10.1016/j.omtn.2020.07.002
MicroRNAs promote skeletal muscle differentiation of mesodermal iPSC-derived progenitors. Giacomazzi Giorgia,Holvoet Bryan,Trenson Sander,Caluwé Ellen,Kravic Bojana,Grosemans Hanne,Cortés-Calabuig Álvaro,Deroose Christophe M,Huylebroeck Danny,Hashemolhosseini Said,Janssens Stefan,McNally Elizabeth,Quattrocelli Mattia,Sampaolesi Maurilio Nature communications Muscular dystrophies (MDs) are often characterized by impairment of both skeletal and cardiac muscle. Regenerative strategies for both compartments therefore constitute a therapeutic avenue. Mesodermal iPSC-derived progenitors (MiPs) can regenerate both striated muscle types simultaneously in mice. Importantly, MiP myogenic propensity is influenced by somatic lineage retention. However, it is still unknown whether human MiPs have in vivo potential. Furthermore, methods to enhance the intrinsic myogenic properties of MiPs are likely needed, given the scope and need to correct large amounts of muscle in the MDs. Here, we document that human MiPs can successfully engraft into the skeletal muscle and hearts of dystrophic mice. Utilizing non-invasive live imaging and selectively induced apoptosis, we report evidence of striated muscle regeneration in vivo in mice by human MiPs. Finally, combining RNA-seq and miRNA-seq data, we define miRNA cocktails that promote the myogenic potential of human MiPs. 10.1038/s41467-017-01359-w
promoter-associated lncRNA is essential for myogenic differentiation. Hitachi Keisuke,Nakatani Masashi,Takasaki Akihiko,Ouchi Yuya,Uezumi Akiyoshi,Ageta Hiroshi,Inagaki Hidehito,Kurahashi Hiroki,Tsuchida Kunihiro EMBO reports Promoter-associated long non-coding RNAs (lncRNAs) regulate the expression of adjacent genes; however, precise roles of these lncRNAs in skeletal muscle remain largely unknown. Here, we characterize a promoter-associated lncRNA, , in myogenic differentiation and muscle disorders. is expressed from the promoter region of the mouse and human gene, one of the key myogenic transcription factors. We show that is essential both for the specification of myoblasts by activating neighboring expression and for myoblast cell cycle withdrawal by activating myogenic microRNA expression. Mechanistically, interacts with Ddx17, a transcriptional coactivator of MyoD, and regulates the association between Ddx17 and the histone acetyltransferase PCAF also promotes skeletal muscle atrophy caused by denervation, and knockdown of rescues muscle wasting in mice. Our findings demonstrate that is a novel key regulator of muscle development and suggest that is a potential therapeutic target for neurogenic atrophy in humans. 10.15252/embr.201847468
Lnc-mg is a long non-coding RNA that promotes myogenesis. Zhu Mu,Liu Jiafan,Xiao Jia,Yang Li,Cai Mingxiang,Shen Hongyu,Chen Xiaojia,Ma Yi,Hu Sumin,Wang Zuolin,Hong An,Li Yingxian,Sun Yao,Wang Xiaogang Nature communications Recent studies indicate important roles for long noncoding RNAs (lncRNAs) as essential regulators of myogenesis and adult skeletal muscle regeneration. However, the specific roles of lncRNAs in myogenic differentiation of adult skeletal muscle stem cells and myogenesis are still largely unknown. Here we identify a lncRNA that is specifically enriched in skeletal muscle (myogenesis-associated lncRNA, in short, lnc-mg). In mice, conditional knockout of lnc-mg in skeletal muscle results in muscle atrophy and the loss of muscular endurance during exercise. Alternatively, skeletal muscle-specific overexpression of lnc-mg promotes muscle hypertrophy. In vitro analysis of primary skeletal muscle cells shows that lnc-mg increases gradually during myogenic differentiation and its overexpression improves cell differentiation. Mechanistically, lnc-mg promotes myogenesis, by functioning as a competing endogenous RNA (ceRNA) for microRNA-125b to control protein abundance of insulin-like growth factor 2. These findings identify lnc-mg as a novel noncoding regulator for muscle cell differentiation and skeletal muscle development. 10.1038/ncomms14718
The H19 long noncoding RNA gives rise to microRNAs miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration. Dey Bijan K,Pfeifer Karl,Dutta Anindya Genes & development Regulated expression of the H19 long noncoding RNA gene has been well characterized as a paradigm for genomic imprinting, but the H19 RNA's biological function remains largely unclear. H19 is abundantly expressed maternally in embryonic tissues but is strongly repressed after birth, and significant transcription persists only in skeletal muscle. Thus, we examined the role of the H19 RNA in skeletal muscle differentiation and regeneration. Knockdown of H19 RNA in myoblast cells and H19 knockout mouse satellite cells decreases differentiation. H19 exon1 encodes two conserved microRNAs, miR-675-3p and miR-675-5p, both of which are induced during skeletal muscle differentiation. The inhibition of myogenesis by H19 depletion during myoblast differentiation is rescued by exogenous expression of miR-675-3p and miR-675-5p. H19-deficient mice display abnormal skeletal muscle regeneration after injury, which is rectified by reintroduction of miR-675-3p and miR-675-5p. miR-675-3p and miR-675-5p function by directly targeting and down-regulating the anti-differentiation Smad transcription factors critical for the bone morphogenetic protein (BMP) pathway and the DNA replication initiation factor Cdc6. Therefore, the H19 long noncoding RNA has a critical trans-regulatory function in skeletal muscle differentiation and regeneration that is mediated by the microRNAs encoded within H19. 10.1101/gad.234419.113