Spaceflight-Associated Changes of snoRNAs in Peripheral Blood Mononuclear Cells and Plasma Exosomes—A Pilot Study

Amit Kumar Rai, K. Shanmugha Rajan, Malik Bisserier, Agnieszka Brojakowska, Aimy Sebastian, Angela C. Evans, Matthew A. Coleman, Paul J. Mills, Arsen Arakelyan, Shizuka Uchida, Lahouaria Hadri, David A. Goukassian, Venkata Naga Srikanth Garikipati

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

During spaceflight, astronauts are exposed to various physiological and psychological stressors that have been associated with adverse health effects. Therefore, there is an unmet need to develop novel diagnostic tools to predict early alterations in astronauts’ health. Small nucleolar RNA (snoRNA) is a type of short non-coding RNA (60–300 nucleotides) known to guide 2′-O-methylation (Nm) or pseudouridine (ψ) of ribosomal RNA (rRNA), small nuclear RNA (snRNA), or messenger RNA (mRNA). Emerging evidence suggests that dysregulated snoRNAs may be key players in regulating fundamental cellular mechanisms and in the pathogenesis of cancer, heart, and neurological disease. Therefore, we sought to determine whether the spaceflight-induced snoRNA changes in astronaut’s peripheral blood (PB) plasma extracellular vesicles (PB-EV) and peripheral blood mononuclear cells (PBMCs). Using unbiased small RNA sequencing (sRNAseq), we evaluated changes in PB-EV snoRNA content isolated from astronauts (n = 5/group) who underwent median 12-day long Shuttle missions between 1998 and 2001. Using stringent cutoff (fold change > 2 or log2-fold change >1, FDR < 0.05), we detected 21 down-and 9—up-regulated snoRNAs in PB-EVs 3 days after return (R + 3) compared to 10 days before launch (L-10). qPCR validation revealed that SNORA74A was significantly down-regulated at R + 3 compared to L-10. We next determined snoRNA expression levels in astronauts’ PBMCs at R + 3 and L-10 (n = 6/group). qPCR analysis further confirmed a significant increase in SNORA19 and SNORA47 in astronauts’ PBMCs at R + 3 compared to L-10. Notably, many downregulated snoRNA-guided rRNA modifications, including four Nms and five ψs. Our findings revealed that spaceflight induced changes in PB-EV and PBMCs snoRNA expression, thus suggesting snoRNAs may serve as potential novel biomarkers for monitoring astronauts’ health.

Original languageEnglish
Article number886689
JournalFrontiers in Cardiovascular Medicine
Volume9
DOIs
StatePublished - 24 Jun 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2022 Rai, Rajan, Bisserier, Brojakowska, Sebastian, Evans, Coleman, Mills, Arakelyan, Uchida, Hadri, Goukassian and Garikipati.

Funding

This work was supported by the Translational Research Institute for Space Health FIP0005 and National Aeronautics and Space Administration grant 80NSSC19K1079 to DAG. This work was also partially supported by American Heart Association Career Development Award 18CDA34110277 and startup funds from the Ohio State University Medical Center to VNSG. AKR was supported with the American Heart Association-Post Doctoral Fellowship grant 915681. KSR was supported by Koshland Foundation and Dean of Chemistry, Postdoctoral Excellence Fellowship. Work was also performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344.

FundersFunder number
Ohio State University Medical Center
Translational Research Institute for Space HealthFIP0005
U.S. Department of Energy
National Aeronautics and Space Administration80NSSC19K1079
American Heart Association915681, 18CDA34110277
Lawrence Livermore National LaboratoryDE-AC52-07NA27344
Koshland Foundation

    Keywords

    • astronaut
    • biomarker
    • extracellular vesicles
    • peripheral blood—mononuclear cells
    • snoRNA

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