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The mammalian LINC complex component SUN1 regulates muscle regeneration by modulating drosha activity.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Ye, Xiaoqian 
Chai, Ruth Jinfen 
Ito, Mitsuteru 
Bonne, Gisèle 

Abstract

Here we show that a major muscle specific isoform of the murine LINC complex protein SUN1 is required for efficient muscle regeneration. The nucleoplasmic domain of the isoform specifically binds to and inhibits Drosha, a key component of the microprocessor complex required for miRNA synthesis. Comparison of the miRNA profiles between wildtype and SUN1 null myotubes identified a cluster of miRNAs encoded by a non-translated retrotransposon-like one antisense (Rtl1as) transcript that are decreased in the WT myoblasts due to SUN1 inhibition of Drosha. One of these miRNAs miR-127 inhibits the translation of the Rtl1 sense transcript, that encodes the retrotransposon-like one protein (RTL1), which is also required for muscle regeneration and is expressed in regenerating/dystrophic muscle. The LINC complex may therefore regulate gene expression during muscle regeneration by controlling miRNA processing. This provides new insights into the molecular pathology underlying muscular dystrophies and how the LINC complex may regulate mechanosignaling.

Description

Keywords

Drosha, LINC complex, RTL1, Sun1, cell biology, human, mouse, muscle fiber, regeneration, Animals, Mice, Microtubule-Associated Proteins, Muscles, RNA, Long Noncoding, Regeneration, Ribonuclease III

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

8

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Medical Research Council (MR/R009791/1)