An essential role for the piRNA pathway in regulating the ribosomal RNA pool in C. elegans

Piwi-interacting RNAs (piRNAs) are RNA effectors with key roles in maintaining genome integrity and promoting fertility in metazoans. In Caenorhabditis elegans loss of piRNAs leads to a transgenerational sterility phenotype. The plethora of piRNAs and their ability to silence transcripts with imperfect complementarity have raised several (non-exclusive) models for the underlying drivers of sterility. Here, we report the extranuclear and transferable nature of the sterility driver, its suppression via mutations disrupting the endogenous RNAi and poly-uridylation machinery, and copy-number amplification at the ribosomal DNA locus. In piRNA-deficient animals, several small interfering RNA (siRNA) populations become increasingly overabundant in the generations preceding loss of germline function, including ribosomal siRNAs (risiRNAs). A concomitant increase in uridylated sense rRNA fragments suggests that poly-uridylation may potentiate RNAi-mediated gene silencing of rRNAs. We conclude that loss of the piRNA machinery allows for unchecked amplification of siRNA populations, originating from abundant highly structured RNAs, to deleterious levels.

Automated summary

Piwi-interacting RNAs (piRNAs) are RNA effectors that play key roles in maintaining genome integrity and promoting fertility in metazoans. Loss of piRNAs in Caenorhabditis elegans results in a transgenerational sterility phenotype. The study reveals that in piRNA-deficient animals, various small interfering RNA (siRNA) populations, including ribosomal siRNAs (risiRNAs), become increasingly overabundant in the generations before loss of germline function. Poly-uridylation may potentiate RNAi-mediated gene silencing of rRNAs. Loss of the piRNA machinery leads to unchecked amplification of siRNA populations, originating from abundant highly structured RNAs, to deleterious levels.