miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis

  1. Elik Chapnik
  2. Natalia Rivkin
  3. Alexander Mildner
  4. Gilad Beck
  5. Ronit Pasvolsky
  6. Eyal Metzl-Raz
  7. Yehudit Birger
  8. Gail Amir
  9. Itay Tirosh
  10. Ziv Porat
  11. Liron L Israel
  12. Emmanuel Lellouche
  13. Shulamit Michaeli
  14. Jean-paul M Lellouche
  15. Shai Izraeli
  16. Steffen Jung
  17. Eran Hornstein  Is a corresponding author
  1. Weizmann Institute of Science, Israel
  2. Tel Aviv University, Israel
  3. Hadassah Medical Center, Israel
  4. Bar-Ilan University, Israel

Abstract

Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer that controls the differentiation and function of various cellular systems, including hematopoietic cells. miR-142 is one of the most prevalently expressed miRNAs within the hematopoietic lineage. To address the in vivo functions of miR-142 we utilized a novel reporter and loss-of-function mouse allele that we have recently generated. Here, we show that miR-142 is broadly expressed in the adult hematopoietic system. Our data further reveal that miR-142 is critical for megakaryopoiesis. Thus, genetic miR-142 ablation caused impaired megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia. Finally, we characterize a network of miR-142-3p targets which collectively controls actin filament homeostasis, thereby ensuring proper execution of actin-dependent proplatelet formation. Our study reveals a pivotal role for miR-142 activity in megakaryocyte maturation and function, and demonstrates a critical contribution of a single miRNA in orchestrating cytoskeletal dynamics and normal haemostasis.

Article and author information

Author details

  1. Elik Chapnik

    Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Natalia Rivkin

    Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexander Mildner

    Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Gilad Beck

    Weizmann Institute of Science, Revhovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Ronit Pasvolsky

    Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Eyal Metzl-Raz

    Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Yehudit Birger

    Tel Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  8. Gail Amir

    Hadassah Medical Center, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  9. Itay Tirosh

    Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  10. Ziv Porat

    Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  11. Liron L Israel

    Bar-Ilan University, Ramat-Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  12. Emmanuel Lellouche

    Bar-Ilan University, Ramat-Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  13. Shulamit Michaeli

    Bar-Ilan University, Ramat-Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  14. Jean-paul M Lellouche

    Bar-Ilan University, Ramat-Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  15. Shai Izraeli

    Tel Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  16. Steffen Jung

    Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  17. Eran Hornstein

    Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    eran.hornstein@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.

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) protocol of the Weizmann Instituter of Science. The protocol, entitled "miR-142 in hematopoietic lineage development" was approved under Permit Numbers: 02930513-3 and 00350111-1. Every effort was made to minimize suffering.

Reviewing Editor

  1. Elaine Fuchs, Rockefeller University, United States

Publication history

  1. Received: November 27, 2013
  2. Accepted: May 21, 2014
  3. Accepted Manuscript published: May 23, 2014 (version 1)
  4. Version of Record published: June 24, 2014 (version 2)

Copyright

© 2014, Chapnik 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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  1. Elik Chapnik
  2. Natalia Rivkin
  3. Alexander Mildner
  4. Gilad Beck
  5. Ronit Pasvolsky
  6. Eyal Metzl-Raz
  7. Yehudit Birger
  8. Gail Amir
  9. Itay Tirosh
  10. Ziv Porat
  11. Liron L Israel
  12. Emmanuel Lellouche
  13. Shulamit Michaeli
  14. Jean-paul M Lellouche
  15. Shai Izraeli
  16. Steffen Jung
  17. Eran Hornstein
(2014)
miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis
eLife 3:e01964.
https://doi.org/10.7554/eLife.01964

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