Emerging role of exosomal long non-coding RNAs in spaceflight-associated risks in astronauts

During spaceflight, astronauts are exposed to multiple unique environmental factors, particularly microgravity and ionizing radiation, that can cause a range of harmful health consequences. Over the past decades, increasing evidence demonstrates that the space environment can induce changes in gene expression and RNA processing. Long non-coding RNA (lncRNA) represent an emerging area of focus in molecular biology as they modulate chromatin structure and function, the transcription of neighboring genes, and affect RNA splicing, stability, and translation. They have been implicated in cancer development and associated with diverse cardiovascular conditions and associated risk factors. However, their role on astronauts’ health after spaceflight remains poorly understood.

Researchers at the Icahn School of Medicine at Mount Sinai provide new insights into the potential role of exosomal lncRNA after spaceflight. The researchers analyzed the transcriptional profile of exosomes isolated from peripheral blood plasma of three astronauts who flew on various Shuttle missions between 1998-2001 by RNA-sequencing. Computational analysis of the transcriptome of these exosomes identified 27 differentially expressed lncRNAs with a Log2 fold change, with molecular, cellular, and clinical implications.

Identification of 27 differentially regulated lncRNA in exosomes
from astronauts 3-days post-landing

(A) Schematic representation of the experimental design. Blood was sampled at two different time points: 10 days before launch (L-10) and 3 days after return (R+3) from three different astronauts. Exosomes were isolated from blood plasma, and purified exosomal RNA was analyzed by RNA-Sequencing. (B) Computational analysis identified 27 differentially regulated lncRNA with a Log2 fold change >2, p < 0.001, and FDR <0.05, compared to baseline L-10. (C) Volcano plots showing Log2-fold changes for the 27 differentially regulated lncRNA and the statistical significance of each gene calculated after DEG analysis. Red points indicate significantly down-regulated genes; green points indicate up-regulated genes. (D) Chromosomal location of the lncRNA is shown. (E) Normalized counts, or the number of reads that align to a particular feature after correcting for sequencing depth and transcriptome composition bias, are shown for the top 5 up-regulated and down-regulated lncRNA in astronauts at L-10 and R+3.

Bisserier M, Saffran N, Brojakowska A, Sebastian A, Evans AC, Coleman MA, Walsh K, Mills PJ, Garikipati VNS, Arakelyan A, Hadri L, Goukassian DA. (2022) Emerging Role of Exosomal Long Non-coding RNAs in Spaceflight-Associated Risks in Astronauts. Front Genet 12:812188. [article]

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