Characterization of all small RNAs in and comparisons across cultured megakaryocytes and platelets of healthy individuals and COVID-19 patients.
Publication/Presentation Date
11-1-2023
Abstract
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
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.
Volume
21
Issue
11
First Page
3252
Last Page
3267
ISSN
1538-7836
Published In/Presented At
Nersisyan, S., Montenont, E., Loher, P., Middleton, E. A., Campbell, R., Bray, P., & Rigoutsos, I. (2023). Characterization of all small RNAs in and comparisons across cultured megakaryocytes and platelets of healthy individuals and COVID-19 patients. Journal of thrombosis and haemostasis : JTH, 21(11), 3252–3267. https://doi.org/10.1016/j.jtha.2023.07.028
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
37558133
Department(s)
Administration and Leadership
Document Type
Article