在太空飞行期间，宇航员面临各种生理和心理压力，这些压力与不利的健康影响有关。因此,开发新的诊断工具来预测宇航员健康的早期变化还没有得到满足。小核仁RNA（snoRNA）是一种短非编码RNA（60-300个核苷酸），已知可指导核糖体RNA（rRNA）的2'-O-甲基化（Nm）或假尿苷（Φ），小核RNA（snRNA），或信使RNA（mRNA）。新的证据表明，失调的snoRNAs可能是调节基本细胞机制和癌症发病机制的关键角色。心,和神经系统疾病。因此,我们试图确定航天飞行诱导的snoRNA是否在宇航员外周血(PB)血浆细胞外囊泡(PB-EV)和外周血单核细胞(PBMC)中发生变化.使用无偏小RNA测序（sRNAseq），我们评估了从1998年至2001年接受中位12天穿梭任务的宇航员(n=5/组)中分离出的PB-EVsnoRNA含量的变化.使用严格的截止值（倍数变化>2或log2倍变化>1，FDR<0.05），与启动前10天(L-10)相比,我们在返回后3天(R+3)在PB-EV中检测到21个下调和9个上调的snoRNAs.qPCR验证显示,与L-10相比,SNORA74A在R+3处显著下调。接下来，我们确定了宇航员PBMC中R3和L-10的snoRNA表达水平（n=6/组）。qPCR分析进一步证实,与L-10相比,在R+3的宇航员PBMC中SNORA19和SNORA47显著增加。值得注意的是,许多下调的snoRNA引导的rRNA修饰，包括4个Nms和5个Φs。我们的发现表明，太空飞行诱导PB-EV和PBMCssnoRNA表达的变化，因此表明snoRNAs可能作为监测宇航员健康的潜在新型生物标志物。
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.
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