MicroRNAs involved in the control of toxicity on locomotion behavior induced by simulated microgravity stress in Caenorhabditis elegans

Lingmei Sun,Dan Li,Wenjie Li,Dayong Wang

doi:10.1038/s41598-020-74582-z

Abstract

microRNAs (miRNAs) post-transcriptionally regulate the expression of targeted genes. We here systematically identify miRNAs in response to simulated microgravity based on both expressions and functional analysis in Caenorhabditis elegans. After simulated microgravity treatment, we observed that 19 miRNAs (16 down-regulated and 3 up-regulated) were dysregulated. Among these dysregulated miRNAs, let-7, mir-54, mir-67, mir-85, mir-252, mir-354, mir-789, mir-2208, and mir-5592 were required for the toxicity induction of simulated microgravity in suppressing locomotion behavior. In nematodes, alteration in expressions of let-7, mir-67, mir-85, mir-252, mir-354, mir-789, mir-2208, and mir-5592 mediated a protective response to simulated microgravity, whereas alteration in mir-54 expression mediated the toxicity induction of simulated microgravity. Moreover, among these candidate miRNAs, let-7 regulated the toxicity of simulated microgravity by targeting and suppressing SKN-1/Nrf protein. In the intestine, a signaling cascade of SKN-1/Nrf-GST-4/GST-5/GST-7 required for the control of oxidative stress was identified to act downstream of let-7 to regulate the toxicity of simulated microgravity. Our data demonstrated the crucial function of miRNAs in regulating the toxicity of simulated microgravity stress in organisms. Moreover, our results further provided an important molecular basis for epigenetic control of toxicity of simulated microgravity.

Highlights

MicroRNAs post-transcriptionally regulate the expression of targeted genes
After simulated microgravity treatment in Rotary Cell Culture System (RCCS) system at 30 rpm and for 24 h, we identified 19 dysregulated miRNAs based on the SOLiD sequencing (Fig. 1 and Table S1)
To confirm the role of these miRNAs in affecting the toxicity of simulated microgravity, we investigated the effects of mir-67, mir-77, mir-78, mir-85, mir-252, mir-52, mir-51, or let-7 mutation on locomotion behavior in simulated microgravity treated nematodes

Summary

Introduction

We here systematically identify miRNAs in response to simulated microgravity based on both expressions and functional analysis in Caenorhabditis elegans. We observed that 19 miRNAs (16 down-regulated and 3 up-regulated) were dysregulated Among these dysregulated miRNAs, let-7, mir-54, mir-67, mir-85, mir-252, mir-354, mir-789, mir-2208, and mir-5592 were required for the toxicity induction of simulated microgravity in suppressing locomotion behavior. Alteration in expressions of let-7, mir-67, mir-85, mir-252, mir-354, mir-789, mir-2208, and mir-5592 mediated a protective response to simulated microgravity, whereas alteration in mir[54] expression mediated the toxicity induction of simulated microgravity Among these candidate miRNAs, let-7 regulated the toxicity of simulated microgravity by targeting and suppressing SKN-1/Nrf protein. We here used C. elegans to systematically identify miRNAs involved in the control of toxicity of simulated microgravity stress on locomotion. Our data provided the molecular basis for our understanding the miRNAs-mediated epigenetic control of toxicity of simulated microgravity in nematodes

Methods

Results

Conclusion