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miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis
oleh: 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
Format: | Article |
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Diterbitkan: | eLife Sciences Publications Ltd 2014-05-01 |
Deskripsi
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.