Diverse functions of homologous actin isoforms are defined by their nucleotide, rather than their amino acid sequence

  1. Pavan Vedula
  2. Satoshi Kurosaka
  3. Nicolae Adrian Leu
  4. Yuri I Wolf
  5. Svetlana A Shabalina
  6. Junling Wang
  7. Stephanie Sterling
  8. Dawei Dong
  9. Anna Kashina  Is a corresponding author
  1. University of Pennsylvania, United States
  2. National Institutes of Health, United States

Abstract

β‐ and γ‐cytoplasmic actin are nearly indistinguishable in their amino acid sequence, but are encoded by different genes that play non‐redundant biological roles. The key determinants that drive their functional distinction are unknown. Here we tested the hypothesis that β- and γ-actin functions are defined by their nucleotide, rather than their amino acid sequence, using targeted editing of the mouse genome. Although previous studies have shown that disruption of β-actin gene critically impacts cell migration and mouse embryogenesis, we demonstrate here that generation of a mouse lacking β-actin protein by editing β-actin gene to encode γ-actin protein, and vice versa, does not affect cell migration and/or organism survival. Our data suggest that the essential in vivo function of β-actin is provided by the gene sequence independent of the encoded protein isoform. We propose that this regulation constitutes a global 'silent code' mechanism that controls the functional diversity of protein isoforms.

Data availability

The following previously published data sets were used

Article and author information

Author details

  1. Pavan Vedula

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9914-0008
  2. Satoshi Kurosaka

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4365-9003
  3. Nicolae Adrian Leu

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yuri I Wolf

    National Center for Biotechnology Information, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Svetlana A Shabalina

    National Center for Biotechnology Information, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Junling Wang

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Stephanie Sterling

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Dawei Dong

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Anna Kashina

    Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, United States
    For correspondence
    akashina@upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0243-6866

Funding

National Institutes of Health (GM104003)

  • Anna Kashina

National Institutes of Health (GM117984)

  • Anna Kashina

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#805204) of the University of Pennsylvania.

Reviewing Editor

  1. Pekka Lappalainen, University of Helsinki, Finland

Publication history

  1. Received: August 31, 2017
  2. Accepted: December 13, 2017
  3. Accepted Manuscript published: December 15, 2017 (version 1)
  4. Version of Record published: February 1, 2018 (version 2)
  5. Version of Record updated: February 26, 2018 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Pavan Vedula
  2. Satoshi Kurosaka
  3. Nicolae Adrian Leu
  4. Yuri I Wolf
  5. Svetlana A Shabalina
  6. Junling Wang
  7. Stephanie Sterling
  8. Dawei Dong
  9. Anna Kashina
(2017)
Diverse functions of homologous actin isoforms are defined by their nucleotide, rather than their amino acid sequence
eLife 6:e31661.
https://doi.org/10.7554/eLife.31661
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