miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL
1
Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, China
2
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; https://doi.org/10.3390/ijms17020182
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.
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Keywords:
miR-30-5p; muscle differentiation; MBNL; myotonic dystrophy
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MDPI and ACS Style
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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