title: miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis.
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.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Elik
authors.initials: E
authors.lastname: Chapnik
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Natalia
authors.initials: N
authors.lastname: Rivkin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Gilad
authors.initials: G
authors.lastname: Beck
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Pasvolsky
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Metzl-Raz
authors.affiliation: Functional Genomics and Leukemic Research, Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Birger
authors.affiliation: Department of Pathology, Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Gail
authors.initials: G
authors.lastname: Amir
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Tirosh
authors.affiliation: Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Porat
authors.affiliation: Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Liron L
authors.initials: LL
authors.lastname: Israel
authors.affiliation: 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.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lellouche
authors.affiliation: 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.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Michaeli
authors.affiliation: Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Jean-Paul M
authors.initials: JP
authors.lastname: Lellouche
authors.affiliation: 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.
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel eran.hornstein@weizmann.ac.il.
authors.forename: Eran
authors.initials: E
authors.lastname: Hornstein
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D057809:HEK293 Cells; D006487:Hemostasis; D006706:Homeostasis; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction; D013921:Thrombocytopenia / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D034061:Thrombopoiesis / Q000235:genetics; D014162:Transfection
chemical_list: D003598:Cytoskeletal Proteins; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse
keywords: actin; cytoskeleton; megakaryocytes; megakaryopoiesis; miR-142; microRNA