The mammalian LINC complex component SUN1 regulates muscle regeneration by modulating Drosha activity
- Institute of Medical Biology, Singapore
- University of Cambridge, United Kingdom
- INSERM UMRS 974, France
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 1 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 1 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures
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Author details
Funding
National Medical Research Council (NMRC/TCR/006-NUHS/2013)
- Colin L Stewart
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Mice were maintained at the A*STAR Biological Resource Centre facility in accordance with the guidelines of the IACUC committee. Experimental procedures were performed under the protocol number IUCAC #181326.
Copyright
© 2019, Loo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The mammalian LINC complex component SUN1 regulates muscle regeneration by modulating Drosha activity
eLife 8:e49485.
https://doi.org/10.7554/eLife.49485
