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

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 profi...

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Main Authors: Zhang, Bo-Wen, Cai, Han-Fang, Wei, Xue-Feng, Sun, Jia-Jie, Lan, Xian-Yong, Lei, Chu-Zhao, Lin, Feng-Peng, Qi, Xing-Lei, Plath, Martin, Chen, Hong
Format: Online
Language:English
Published: MDPI 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783916/
id pubmed-4783916
recordtype oai_dc
spelling pubmed-47839162016-03-14 miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL Zhang, Bo-Wen Cai, Han-Fang Wei, Xue-Feng Sun, Jia-Jie Lan, Xian-Yong Lei, Chu-Zhao Lin, Feng-Peng Qi, Xing-Lei Plath, Martin Chen, Hong Article 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. MDPI 2016-01-29 /pmc/articles/PMC4783916/ /pubmed/26840300 http://dx.doi.org/10.3390/ijms17020182 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Zhang, Bo-Wen
Cai, Han-Fang
Wei, Xue-Feng
Sun, Jia-Jie
Lan, Xian-Yong
Lei, Chu-Zhao
Lin, Feng-Peng
Qi, Xing-Lei
Plath, Martin
Chen, Hong
spellingShingle Zhang, Bo-Wen
Cai, Han-Fang
Wei, Xue-Feng
Sun, Jia-Jie
Lan, Xian-Yong
Lei, Chu-Zhao
Lin, Feng-Peng
Qi, Xing-Lei
Plath, Martin
Chen, Hong
miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL
author_facet Zhang, Bo-Wen
Cai, Han-Fang
Wei, Xue-Feng
Sun, Jia-Jie
Lan, Xian-Yong
Lei, Chu-Zhao
Lin, Feng-Peng
Qi, Xing-Lei
Plath, Martin
Chen, Hong
author_sort Zhang, Bo-Wen
title miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL
title_short miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL
title_full miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL
title_fullStr miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL
title_full_unstemmed miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle-Related Genes by Targeting MBNL
title_sort mir-30-5p regulates muscle differentiation and alternative splicing of muscle-related genes by targeting mbnl
description 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.
publisher MDPI
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783916/
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