Abstract P1115: SnoRNAs As Potential Biomarkers For Assessment Of Health Risks In Astronauts

Abstract

During spaceflight, astronauts are exposed to various physiological and psychological stressors, such as microgravity, sleep deprivation, isolation, confinement, and high ionizing radiation have shown 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 ncRNAs (60-300 nucleotides) known to guide 2’-O-methylation (Nm) or pseudouridine (ψ) on ribosomal RNA (rRNA), snRNA, or mRNA. Emerging evidence suggests that dysregulated snoRNAs may be key players in regulating fundamental cellular mechanisms and the pathogenesis of cancer, heart, and neurological disease. Therefore, we sought to determine whether the spaceflight-induced snoRNA changes in plasma extracellular vesicles (EV) and astronaut's peripheral blood mononuclear cells (PBMCs) can be utilized as potential biomarkers. Using unbiased small RNA sequencing (sRNAseq), we evaluated the EV snoRNA changes in peripheral blood (PB) plasma of astronauts (n=5/group) who underwent median 12-day long Shuttle missions between 1998-2001. Using stringent cutoff (> log 2-fold change, FDR < 0.05), we detected 20 down-regulated snoRNAs and 10 upregulated PB-EVs at R+3 compared to 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 unveiled that spaceflight induced changes in EV and PBMCs snoRNA expression, thus suggesting snoRNAs may serve as novel biomarkers for monitoring astronauts' health.