miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis
Elik Chapnik,
Natalia Rivkin,
Alexander Mildner,
Gilad Beck,
Ronit Pasvolsky,
Eyal Metzl-Raz,
Yehudit Birger,
Gail Amir,
Itay Tirosh,
Ziv Porat,
Liron L Israel,
Emmanuel Lellouche,
Shulamit Michaeli,
Jean-Paul M Lellouche,
Shai Izraeli,
Steffen Jung,
Eran Hornstein
Affiliations
Elik Chapnik
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Natalia Rivkin
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Alexander Mildner
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Gilad Beck
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Ronit Pasvolsky
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Eyal Metzl-Raz
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Yehudit Birger
Functional Genomics and Leukemic Research, Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel
Gail Amir
Department of Pathology, Hadassah Medical Center, Jerusalem, Israel
Itay Tirosh
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Ziv Porat
Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel
Liron L Israel
Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel; Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel
Emmanuel Lellouche
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
Shulamit Michaeli
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
Jean-Paul M Lellouche
Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel; Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel
Shai Izraeli
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
Steffen Jung
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Eran Hornstein
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
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.
