miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL |
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Authors: | Bo-Wen Zhang Han-Fang Cai Xue-Feng Wei Jia-Jie Sun Xian-Yong Lan Chu-Zhao Lei Feng-Peng Lin Xing-Lei Qi Martin Plath Hong Chen |
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Affiliation: | 1.Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, China; (B.-W.Z.); (H.-F.C.); (X.-F.W.); (J.-J.S.); (X.-Y.L.); (C.-Z.L.); (M.P.);2.Department of Animal Husbandry, Bureau of Biyang County of Henan province, Biyang 463700, Henan, China; (F.-P.L.); (X.-L.Q.) |
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Abstract: | MicroRNAs (miRNAs), a class of single stranded, small (~22 nucleotides), non-coding RNAs, play an important role in muscle development. We focused on the role of the miR-30-5p family during bovine muscle development from previous high-throughput sequencing results and analyzed their expression profiles. MHC and MyoG mRNAs expression as well as their proteins were suppressed in differentiated C2C12 cells, suggesting the importance of miR-30-5p in muscle development. MBNL, the candidate target of miR-30-5p, is an alternative splicing regulation factor. MBNL1 and MBNL3 have opposite effects on muscle differentiation. Our results confirmed that miR-30a-5p and miR-30e-5p repress the expression of MBNL1, MBNL2 and MBNL3, whereas miR-30b-5p inhibits MBNL1 and MBNL2 expression. This provides direct evidence that MBNL expression can be flexibly regulated by miR-30-5p. Previous studies showed that MBNL1 promotes exon inclusion of two muscle-related genes (Trim55 and INSR). Through RNA splicing studies, we found that miR-30-5p had an effect on their alternative splicing, which means miR-30-5p via MBNL1 could be integrated into muscle signaling pathways in which INSR or Trim55 are located. In conclusion, miR-30-5p could inhibit muscle cell differentiation and regulate the alternative splicing of Trim55 and INSR by targeting MBNL. These results promote the understanding of the function of miRNAs in muscle development. |
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Keywords: | miR-30-5p muscle differentiation MBNL myotonic dystrophy |
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