1. Cell Biology
Download icon

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

  1. Tsui Han Loo
  2. Xiaoqian Ye
  3. Ruth Jinfen Chai
  4. Mitsuteru Ito
  5. Gisèle Bonne
  6. Anne C Ferguson-Smith
  7. Colin L Stewart  Is a corresponding author
  1. Institute of Medical Biology, Singapore
  2. University of Cambridge, United Kingdom
  3. INSERM UMRS 974, France
Research Article
  • Cited 0
  • Views 235
  • Annotations
Cite this article as: eLife 2019;8:e49485 doi: 10.7554/eLife.49485

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.

Article and author information

Author details

  1. Tsui Han Loo

    Developmental and Regenerative Biology, Institute of Medical Biology, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaoqian Ye

    Developmental and Regenerative Biology, Institute of Medical Biology, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  3. Ruth Jinfen Chai

    Developmental and Regenerative Biology, Institute of Medical Biology, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  4. Mitsuteru Ito

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Gisèle Bonne

    Center of Research in Myology, INSERM UMRS 974, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Anne C Ferguson-Smith

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Colin L Stewart

    Developmental and Regenerative Biology, Institute of Medical Biology, Singapore, Singapore
    For correspondence
    colin.stewart@imb.a-star.edu.sg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4988-536X

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.

Reviewing Editor

  1. Kavitha Sarma, Wistar Institute, United States

Publication history

  1. Received: June 19, 2019
  2. Accepted: October 27, 2019
  3. Accepted Manuscript published: November 5, 2019 (version 1)

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.

Metrics

  • 235
    Page views
  • 60
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)