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miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL

Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, China
Department of Animal Husbandry, Bureau of Biyang County of Henan province, Biyang 463700, Henan, China
Author to whom correspondence should be addressed.
Academic Editors: Nalini Santanam and William Chi-shing Cho
Int. J. Mol. Sci. 2016, 17(2), 182;
Received: 13 November 2015 / Revised: 26 December 2015 / Accepted: 22 January 2016 / Published: 29 January 2016
(This article belongs to the Special Issue MicroRNA in Various Disease States as Biomarkers)
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. View Full-Text
Keywords: miR-30-5p; muscle differentiation; MBNL; myotonic dystrophy miR-30-5p; muscle differentiation; MBNL; myotonic dystrophy
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Zhang, B.-W.; Cai, H.-F.; Wei, X.-F.; Sun, J.-J.; Lan, X.-Y.; Lei, C.-Z.; Lin, F.-P.; Qi, X.-L.; Plath, M.; Chen, H. miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL. Int. J. Mol. Sci. 2016, 17, 182.

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