Abstract
Hematopoietic–specific microRNA-142 is a critical regulator of various blood cell lineages, but its role in erythrocytes is unexplored. Herein, we characterize the impact of microRNA-142 on erythrocyte physiology and molecular cell biology, using a mouse loss-of-func-tion allele. We report that microRNA-142 is required for maintaining the typical erythrocyte biconcave shape and structural resilience, for the normal metabolism of reactive oxygen species, and for overall lifespan. microRNA-142 further controls ACTIN filament homeostasis and membrane skeleton organization. The analyses presented reveal previously unappreciated functions of microRNA-142 and contribute to an emerging view of small RNAs as key players in erythropoiesis. Finally, the work herein demonstrates how a housekeeping network of cytoskeletal regulators can be reshaped by a single micro-RNA denominator in a cell type specific manner.
| Original language | English |
|---|---|
| Pages (from-to) | 676-685 |
| Number of pages | 10 |
| Journal | Haematologica |
| Volume | 102 |
| Issue number | 4 |
| DOIs | |
| State | Published - 31 Mar 2017 |
Bibliographical note
Funding Information:The authors would like to thank Ofira Higfa and Yehudah Melamed for veterinary services and husbandry and Dr. Joseph Lotem for helpful discussions. The work is funded by the Minerva foundation and Minna-James-Heineman Stiftung through Minerva. Work at the Hornstein lab is further funded by an ERC consolidator program, Israel Science Foundation, the Legacy-heritage program, The Bruno and Ilse Frick Foundation for Research on ALS, the ALS Therapy Alliance, The Motor Neurone Disease Association (UK), the Thierry Latran Foundation for ALS research, the ERA-Net for Research Programmes on Rare Diseases (FP7), A. Alfred Taubman through IsrALS, Teva Pharmaceutical Industries Ltd as part of the Israeli National Network of Excellence in Neuroscience (NNE), Yeda-Sela, Yeda-CEO, Israel Ministry of Trade and Industry, Y. Leon Benoziyo Institute for Molecular Medicine, The Kekst Family Institute for Medical Genetics, The David and Fela Shapell Family Center for Genetic Disorders Research, The Crown Human Genome Center, the Nathan, Shirley, Philip and Charlene Vener New Scientist Fund, Julius and Ray Charlestein Foundation, The Fraida Foundation, The Wolfson Family Charitable Trust, The Adelis Foundation, MERCK (UK), Maria Halphen, and the Estates of Fannie Sherr, Lola Asseof and Lilly Fulop. Electron microscopy studies were partially founded by The Moskowitz Center for Nano and Bio-Nano Imaging at WIS. E.H. is Head of The Nella and Leon Benoziyo Center for Neurological Diseases, and the lab is further supported by Dr. Sydney Brenner.
Publisher Copyright:
© 2017 Ferrata Storti Foundation.