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

• Published in: eLife 2014-05, Vol.3, p.e01964-e01964
• Main Authors: Chapnik, Elik, Rivkin, Natalia, Mildner, Alexander, Beck, Gilad, Pasvolsky, Ronit, Metzl-Raz, Eyal, Birger, Yehudit, Amir, Gail, Tirosh, Itay, Porat, Ziv, Israel, Liron L, Lellouche, Emmanuel, Michaeli, Shulamit, Lellouche, Jean-Paul M, Izraeli, Shai, Jung, Steffen, Hornstein, Eran
• Format: Article
• Language: English
• Subjects: Ablation; Actin; Actin Cytoskeleton - metabolism; Animals; Biosynthesis; Blood; Blood platelets; Cell Biology; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Cytoskeleton; Developmental Biology and Stem Cells; Experiments; Gene expression; Gene Expression Regulation; Genomes; Genotype; HEK293 Cells; Hemostasis; Homeostasis; Humans; Laboratories; Medical research; megakaryocytes; Megakaryocytes - metabolism; Megakaryocytes - pathology; megakaryopoiesis; Mice, Inbred C57BL; Mice, Knockout; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; miR-142; miRNA; Phenotype; Polyploidy; Post-transcription; Proteins; RNA Interference; Signal Transduction; Thrombocytopenia; Thrombocytopenia - blood; Thrombocytopenia - genetics; Thrombocytopenia - metabolism; Thrombopoiesis - genetics; Transfection
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.01964

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.