The RNA-binding protein SRSF3 has an essential role in megakaryocyte maturation and platelet production
| Autor: | Pradnya Gangatirkar, Brenda Williams, Belinda B. Guo, Benjamin Cao, Sarah Ellis, Chad K Heazlewood, Madeline Fulton, Mirana Ramialison, Jacinta F. White, Emma C. Josefsson, Huimin Cao, Tanveer Ahmad, Shen Y. Heazlewood, Madara Ratnadiwakara, Monika Mohenska, Minna-Liisa Änkö, Susan K. Nilsson |
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| Přispěvatelé: | Tampere University, BioMediTech |
| Rok vydání: | 2021 |
| Předmět: |
Blood Platelets
Immunology RNA-binding protein Biology Biochemistry Thrombopoiesis Splicing factor Mice Megakaryocyte medicine Animals Platelet RNA Messenger Regulation of gene expression Mice Knockout Serine-Arginine Splicing Factors RNA Cell Biology Hematology Thrombocytopenia Cell biology Haematopoiesis medicine.anatomical_structure 3111 Biomedicine Megakaryocytes |
| Zdroj: | Blood. 139(9) |
| ISSN: | 1528-0020 |
| Popis: | RNA processing is increasingly recognized as a critical control point in the regulation of different hematopoietic lineages including megakaryocytes responsible for the production of platelets. Platelets are anucleate cytoplasts that contain a rich repertoire of RNAs encoding proteins with essential platelet functions derived from the parent megakaryocyte. It is largely unknown how RNA binding proteins contribute to the development and functions of megakaryocytes and platelets. We show that serine-arginine–rich splicing factor 3 (SRSF3) is essential for megakaryocyte maturation and generation of functional platelets. Megakaryocyte-specific deletion of Srsf3 in mice led to macrothrombocytopenia characterized by megakaryocyte maturation arrest, dramatically reduced platelet counts, and abnormally large functionally compromised platelets. SRSF3 deficient megakaryocytes failed to reprogram their transcriptome during maturation and to load platelets with RNAs required for normal platelet function. SRSF3 depletion led to nuclear accumulation of megakaryocyte mRNAs, demonstrating that SRSF3 deploys similar RNA regulatory mechanisms in megakaryocytes as in other cell types. Our study further suggests that SRSF3 plays a role in sorting cytoplasmic megakaryocyte RNAs into platelets and demonstrates how SRSF3-mediated RNA processing forms a central part of megakaryocyte gene regulation. Understanding SRSF3 functions in megakaryocytes and platelets provides key insights into normal thrombopoiesis and platelet pathologies as SRSF3 RNA targets in megakaryocytes are associated with platelet diseases. |
| Databáze: | OpenAIRE |
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