Dataset Information

The RNA-binding protein ATXN2 controls cellular processes during megakaryopoiesis

ABSTRACT: 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 coagulation. Mice deficient for Atxn2 did not display differences in bleeding times, but expression of key surface receptors on platelets, such as ITGB3 (carries the CD61 antigen) and CD31 (PECAM1), were deregulated and platelet aggregation was reduced upon specific triggers.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Megakaryocyte Cell Line

SUBMITTER: Arie Hoogendijk

LAB HEAD: M. van den Biggelaar, PhD

PROVIDER: PXD015823 | Pride | 2020-05-26

REPOSITORIES: Pride

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Publications

The RNA-Binding Protein ATXN2 is Expressed during Megakaryopoiesis and May Control Timing of Gene Expression.

Hansen Marten M Zeddies Sabrina S Meinders Marjolein M di Summa Franca F van Alphen Floris P J FPJ Hoogendijk Arjan J AJ Moore Kat S KS Halbach Melanie M Gutiérrez Laura L van den Biggelaar Maartje M Thijssen-Timmer Daphne C DC Auburger Georg W J GWJ van den Akker Emile E von Lindern Marieke M Rollmann Ewa E

International journal of molecular sciences 20200131 3

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 (ATXN ...[more]

PMID: 32024018

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Project description:MicroRNAs are small non-coding RNAs that regulate cellular development by interfering with mRNA stability and translation. We defined the kinetics of global microRNA expression during the differentiation of murine hematopoietic progenitors into megakaryocytes. Of 435 miRNAs analyzed, 13 were upregulated and 81 were downregulated. Many of these changes are consistent with miRNA profiling studies of human megakaryocytes and platelets, although new patterns also emerged. Among 7 conserved miRNAs that were upregulated most strongly in megakaryocytes, 6 were also induced in the related erythroid lineage. MiR-146a was strongly upregulated during mouse and human megakaryopoiesis, but not erythropoiesis. However, overexpression of miR-146a in mouse bone marrow hematopoietic progenitor populations produced no detectable alterations in megakaryocyte development or platelet production in vivo or in colony assays. Our findings extend the repertoire of differentially regulated miRNAs during murine megakaryopoiesis and provide a useful new dataset for hematopoiesis research. In addition, we show that enforced hematopoietic expression of miR-146a has minimal effects on megakaryopoiesis. These results are compatible with prior studies indicating that miR-146a inhibits megakaryocyte production indirectly by suppressing cytokine production from innate immune cells, but cast doubt on a different study, which suggests that this miRNA inhibits megakaryopoiesis cell-autonomously. Exiqon locked nucleic acid (LNA) microarrays were used to compare microRNA expression in starting populations (ter 119- progenitors) and purified megakaryocytes. Day13.5-14.5 murine fetal livers (strain CD1) were depleted of erythroid cells and cultured with thrombopoietin to generate megakaryocytes. Each total RNA sample (0.5 Î¼g per reaction) was labeled with Hy3 and Hy5 dyes using the Exiqon Power Labeling Kit and automated microarray hybridizations and washes were performed on a Tecan HS4800 station with 20 hr hybridization at 56ÂºC. Dye-swap pairs of three replicate experiments comparing Ter119- fetal liver cells vs. BSA-purified megakaryocytes were co-hybridized to six arrays. The geometric average of the 532 and 635 measurements after normalization was determined for each sample.

Dataset Information

The RNA-binding protein ATXN2 controls cellular processes during megakaryopoiesis

Publications

The RNA-Binding Protein ATXN2 is Expressed during Megakaryopoiesis and May Control Timing of Gene Expression.

Similar Datasets

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