Spaceflight alters expression of microRNA during T-cell activation.
Altered immune function has been demonstrated in astronauts during spaceflights dating back to Apollo and Skylab; this could be a major barrier to long-term space exploration. We tested the hypothesis that spaceflight causes changes in microRNA (miRNA) expression. Human leukocytes were stimulated with mitogens on board the International Space Station using an onboard normal gravity control. Bioinformatics showed that miR-21 was significantly up-regulated 2-fold during early T-cell activation in normal gravity, and gene expression was suppressed under microgravity. This was confirmed using quantitative real-time PCR (n = 4). This is the first report that spaceflight regulates miRNA expression. Global microarray analysis showed significant (P < 0.05) suppression of 85 genes under microgravity conditions compared to normal gravity samples. EGR3, FASLG, BTG2, SPRY2, and TAGAP are biologically confirmed targets and are co-up-regulated with miR-21. These genes share common promoter regions with pre-mir-21; as the miR-21 matures and accumulates, it most likely will inhibit translation of its target genes and limit the immune response. These data suggest that gravity regulates T-cell activation not only by transcription promotion but also by blocking translation via noncoding RNA mechanisms. Moreover, this study suggests that T-cell activation itself may induce a sequence of gene expressions that is self-limited by miR-21.
*Hughes-Fulford Laboratory, Department of Medicine, Metabolism Division, San Francisco Department of Veterans Affairs Medical Center, San Francisco, California, USA; and Northern California Institute for Research and Education, Department of Medicine, and Department of Surgery, University of California, San Francisco, California, USA milliehf@gmail.com.
Millie
M
Hughes-Fulford
*Hughes-Fulford Laboratory, Department of Medicine, Metabolism Division, San Francisco Department of Veterans Affairs Medical Center, San Francisco, California, USA; and Northern California Institute for Research and Education, Department of Medicine, and Department of Surgery, University of California, San Francisco, California, USA.
Tammy T
TT
Chang
*Hughes-Fulford Laboratory, Department of Medicine, Metabolism Division, San Francisco Department of Veterans Affairs Medical Center, San Francisco, California, USA; and Northern California Institute for Research and Education, Department of Medicine, and Department of Surgery, University of California, San Francisco, California, USA.
Emily M
EM
Martinez
*Hughes-Fulford Laboratory, Department of Medicine, Metabolism Division, San Francisco Department of Veterans Affairs Medical Center, San Francisco, California, USA; and Northern California Institute for Research and Education, Department of Medicine, and Department of Surgery, University of California, San Francisco, California, USA.
Chai-Fei
CF
Li
D020413:3' Untranslated Regions; D000328:Adult; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D013026:Space Flight; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism; D014893:Weightlessness; D055815:Young Adult
D020413:3' Untranslated Regions; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors
epigenetics; gene expression; immune response; microgravity