piRNAs safeguard splicing and RNA fidelity during heat shock

Piwi-interacting RNAs (piRNAs) silence transposons and foreign sequences; yet, for poorly understood reasons, they also extensively target endogenous mRNAs. Here, we report a previously unappreciated role for the Caenorhabditis elegans piRNA pathway in RNA quality control: during heat shock, piRNAs generate endogenous antisense RNAs (endo-siRNAs) that associate with RNA Polymerase II and nascent stress-induced RNAs to delay splicing when the spliceosome is compromised, minimizing transcript errors. In the absence of piRNAs, nascent transcripts undergo premature splicing, accumulate errors, and activate nonsense-mediated decay (NMD) to limit the production of aberrant proteins. We propose that by regulating splicing, the piRNA pathway acts alongside NMD as a quality-control system, safeguarding RNA fidelity and proteome integrity with genome defense.