Role of microRNAs in regulating the DNA damage response to ionizing radiation in Caenorhabditis elegans

microRNAs fine-tune the regulation of numerous biological processes by mediating gene expression post-transcriptionally. Mature miRNAs associate with argonaute (AGO) proteins to form the RNA-induced silencing complex (RISC) that binds to and blocks translation of target mRNAs. In our study, we address the function of miRNAs in regulating DNA damage responses in-vivo, by exploiting the nematode model organism Caenorhabditis elegans. Using next-generation sequencing, we obtained miRNA expression profiles of WT worms as well as mutants harboring a loss-of-function deletion of the C. elegans AGO gene alg-2 that display abnormal cell death in response to genotoxic stress. 2.5 hours after exposure to ionizing irradiation, the miRNA transcriptomes of both WT and alg-2(ok304) mutant worms were only mildly altered in comparison to their respective untreated controls. However, irrespective of treatment, alg-2(ok304) mutants exhibited noticeable dysregulation of several miRNA families with known physiological functions. Reduced levels of some of these miRNAs might explain the abnormal DNA damage response of alg-2-deficient C. elegans. Overall design: miRNA expression profiles of adult N2 (WT) and alg-2(ok304) mutant C. elegans 2.5 hours after treatment with 90 Gy of ionizing radiation