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Elife. 2014 May 23;3:e01964. doi: 10.7554/eLife.01964.

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

Author information

1
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
2
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
3
Functional Genomics and Leukemic Research, Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel.
4
Department of Pathology, Hadassah Medical Center, Jerusalem, Israel.
5
Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel.
6
Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel.
7
Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
8
Functional Genomics and Leukemic Research, Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel.
9
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel eran.hornstein@weizmann.ac.il.

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 a loss-of-function mouse allele that we have recently generated. In this study, we show that miR-142 is broadly expressed in the adult hematopoietic system. Our data further reveal that miR-142 is critical for megakaryopoiesis. Genetic ablation of miR-142 caused impaired megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia. Finally, we characterized a network of miR-142-3p targets which collectively control 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 hemostasis.DOI: http://dx.doi.org/10.7554/eLife.01964.001.

KEYWORDS:

actin; cytoskeleton; megakaryocytes; megakaryopoiesis; miR-142; microRNA

PMID:
24859754
PMCID:
PMC4067751
DOI:
10.7554/eLife.01964
[Indexed for MEDLINE]
Free PMC Article
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