TY - JOUR
T1 - The RNA-binding protein ATXN2 is expressed during megakaryopoiesis and may control timing of gene expression
AU - Hansen, Marten
AU - Zeddies, Sabrina
AU - Meinders, Marjolein
AU - di Summa, Franca
AU - Rollmann, Ewa
AU - van Alphen, Floris P. J.
AU - Hoogendijk, Arjan J.
AU - Moore, Kat S.
AU - Halbach, Melanie
AU - Gutiérrez, Laura
AU - van den Biggelaar, Maartje
AU - Thijssen-Timmer, Daphne C.
AU - Auburger, Georg W. J.
AU - van den Akker, Emile
AU - von Lindern, Marieke
N1 - Funding Information: Funding: This work was funded by Sanquin Blood Supply, grant PPOC-09-023/PPOC-15-25p, The Netherlands Genomics Initiative (NGI-MEC), EuroSCA (LSHM-CT-2004-503304), the DFG (AU96/14-1), the Center for Translational Molecular Medicine (http://www.ctmm.nl), project Innovative Coagulation Diagnostics (INCOAG, grant 01C-201), and the Dutch Heart Foundation. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2
Y1 - 2020/2
N2 - Megakaryopoiesis is the process during which megakaryoblasts differentiate to polyploid megakaryocytes that can subsequently shed thousands of platelets in the circulation. Megakaryocytes accumulate mRNA during their maturation, which is required for the correct spatio-temporal production of cytoskeletal proteins, membranes and platelet-specific granules, and for the subsequent shedding of thousands of platelets per cell. Gene expression profiling identified the RNA binding protein ATAXIN2 (ATXN2) as a putative novel regulator of megakaryopoiesis. ATXN2 expression is high in CD34+/CD41+ megakaryoblasts and sharply decreases upon maturation to megakaryocytes. ATXN2 associates with DDX6 suggesting that it may mediate repression of mRNA translation during early megakaryopoiesis. Comparative transcriptome and proteome analysis on megakaryoid cells (MEG-01) with differential ATXN2 expression identified ATXN2 dependent gene expression of mRNA and protein involved in processes linked to hemostasis. Mice deficient for Atxn2 did not display differences in bleeding times, but the expression of key surface receptors on platelets, such as ITGB3 (carries the CD61 antigen) and CD31 (PECAM1), was deregulated and platelet aggregation upon specific triggers was reduced.
AB - Megakaryopoiesis is the process during which megakaryoblasts differentiate to polyploid megakaryocytes that can subsequently shed thousands of platelets in the circulation. Megakaryocytes accumulate mRNA during their maturation, which is required for the correct spatio-temporal production of cytoskeletal proteins, membranes and platelet-specific granules, and for the subsequent shedding of thousands of platelets per cell. Gene expression profiling identified the RNA binding protein ATAXIN2 (ATXN2) as a putative novel regulator of megakaryopoiesis. ATXN2 expression is high in CD34+/CD41+ megakaryoblasts and sharply decreases upon maturation to megakaryocytes. ATXN2 associates with DDX6 suggesting that it may mediate repression of mRNA translation during early megakaryopoiesis. Comparative transcriptome and proteome analysis on megakaryoid cells (MEG-01) with differential ATXN2 expression identified ATXN2 dependent gene expression of mRNA and protein involved in processes linked to hemostasis. Mice deficient for Atxn2 did not display differences in bleeding times, but the expression of key surface receptors on platelets, such as ITGB3 (carries the CD61 antigen) and CD31 (PECAM1), was deregulated and platelet aggregation upon specific triggers was reduced.
KW - ATAXIN2
KW - ATXN2
KW - Hemostasis
KW - ITGB3
KW - MEG-01
KW - MRNA
KW - Megakaryopoiesis
KW - PECAM1
KW - RBP
KW - Translation
UR - http://www.scopus.com/inward/record.url?scp=85079031986&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms21030967
DO - https://doi.org/10.3390/ijms21030967
M3 - Article
C2 - 32024018
SN - 1661-6596
VL - 21
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 3
M1 - 967
ER -