Characterization of all small RNAs in and comparisons across cultured megakaryocytes and platelets of healthy individuals and COVID-19 patients.

Autor:	Nersisyan S; Computational Medicine Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Montenont E; University of Utah Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA., Loher P; Computational Medicine Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Middleton EA; University of Utah Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA; Division of Pulmonary Medicine, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA., Campbell R; University of Utah Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA; Division of General Medicine, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA., Bray P; University of Utah Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA; Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA., Rigoutsos I; Computational Medicine Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address: isidore.rigoutsos@jefferson.edu.
Jazyk:	angličtina
Zdroj:	Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2023 Nov; Vol. 21 (11), pp. 3252-3267. Date of Electronic Publication: 2023 Aug 07.
DOI:	10.1016/j.jtha.2023.07.028
Abstrakt:	Background: The small noncoding RNAs (sncRNAs) in megakaryocytes (MKs) and platelets are not well characterized. Neither is the impact of SARS-CoV-2 infection on the sncRNAs of platelets. Objectives: To investigate the sorting of MK sncRNAs into platelets, and the differences in the platelet sncRNAomes of healthy donors (HDs) and COVID-19 patients. Methods: We comprehensively profiled sncRNAs from MKs cultured from cord blood-derived CD34 + cells, platelets from HDs, and platelets from patients with moderate and severe SARS-CoV-2 infection. We also comprehensively profiled Argonaute (AGO)-bound sncRNAs from the cultured MKs. Results: We characterized the sncRNAs in MKs and platelets and can account for ∼95% of all sequenced reads. We found that MKs primarily comprise microRNA isoforms (isomiRs), tRNA-derived fragments (tRFs), rRNA-derived fragments (rRFs), and Y RNA-derived fragments (yRFs) in comparable abundances. The platelets of HDs showed a skewed distribution by comparison: 56.7% of all sncRNAs are yRFs, 34.4% are isomiRs, and <2.0% are tRFs and rRFs. Most isomiRs in MKs and platelets are either noncanonical, nontemplated, or both. When comparing MKs and platelets from HDs, we found numerous isomiRs, tRFs, rRFs, and yRFs showing opposite enrichments or depletions, including molecules from the same parental miRNA arm, tRNA, rRNA, or Y RNA. The sncRNAome of platelets from patients with COVID-19 is skewed compared to that of HDs with only 19.8% of all sncRNAs now being yRFs, isomiRs increasing to 63.6%, and tRFs and rRFs more than tripling their presence to 6.1%. Conclusion: The sncRNAomes of MKs and platelets are very rich and more complex than it has been believed. The evidence suggests complex mechanisms that sort MK sncRNAs into platelets. SARS-CoV-2 infection acutely alters the contents of platelets by changing the relative proportions of their sncRNAs. Competing Interests: Declaration of competing interests There are no competing interests to disclose. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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