Integrated Analysis of MRNA and MiRNA Expression Profiles in dys-1 Mutants of C. Elegans After Spaceflight and Simulated Microgravity

Abstract

Dystrophin-like dys-1 gene is expressed and required in muscle tissue, playing a vital role in gravisensing in Caenorhabditis elegans (C. elegans). To date, microRNA (miRNA)-mediated epigenetic mechanism in microgravity-induced muscular atrophy remains to be elucidated. In the present study, we first analyzed mRNA and miRNA expression profiles in space-flown dys-1(cx18) mutants and wild type worms (wt) of C. elegans. The results showed that spaceflight and microgravity have fewer effects on mRNA and miRNA expression in dys-1 mutant than in wt worms. mRNA and miRNA expression patterns of dys-1 mutants were changed by microgravity. Hierarchical clustering analysis showed that the alterations of genes function on neuromuscular system under space environment. Seven miRNAs (cel-miR-52, 56, 81, 82, 84, 124 and 230) have 18 significant anti-correlated target genes under space environment. RT-qPCR analysis confirmed that miR-52 and cdh-3, miR-84 and lin-14, miR-124 and mgl-3 in dys-1 mutants reversely altered under microgravity environment and in simulated microgravity experiment. Locomotion ability was only reduced in F0 wt worms but not in dys-1 mutants as well as their F1 offspring after simulated microgravity. We observed expression alterations of 7 neuromuscular genes (unc-27, nlp-22, flp-1, egl-5, flp-4, mgl-3, unc-94) in F0 wt worms, which might be involved in the regulation of locomotion ability of C. elegans. This study provides important insights to reveal the mechanism in the pathogenesis of muscular atrophy induced by microgravity.