A germline-targeted genetic screen for xrn-2 suppressors identifies a novel gene C34C12.2 in Caenorhabditis elegans

Abstract XRN2 is an evolutionarily conserved 5’-to-3’ exoribonuclease, which degrades or trims various types of RNA in the nucleus. Although XRN-2 is essential for embryogenesis, larval development and reproduction in Caenorhabditis elegans, relevant molecular pathways remain unidentified. Here we create a germline-specific xrn-2 conditional mutant and perform a mutagenesis screen for suppressors of sterility. Loss-of-function alleles of dpy-10, osr-1, ptr-6 and C34C12.2 genes are identified. Depletion of DPY-10, OSR-1 or PTR-6 increases expression of gpdh-1 that encodes a glycerol-3-phosphate dehydrogenase, thereby elevates glycerol accumulation to suppress sterility of the mutant. The C34C12.2 protein is predominantly localized in the nucleolus of germ cells and shows a similarity to Saccharomyces cerevisiae Net1, which is involved in rDNA silencing. Depletion of NRDE-2, a putative interacting partner of C34C12.2 and a component of the nuclear RNAi machinery, restores fertility to the xrn-2 conditional mutant. These results may help to identify an essential role of XRN-2 in germline development.