piRNAs prevent runaway amplification of siRNAs from ribosomal RNAs and histone mRNAs

Abstract

Piwi-interacting RNAs (piRNAs) are a largely germline-specific class of small RNAs found in animals.Although piRNAs are best known for silencing transposons, they regulate many different biological processes. Here we identify a role for piRNAs in preventing runaway amplification of small interfering RNAs (siRNAs) from certain genes, including ribosomal RNAs (rRNAs) and histone mRNAs. In Caenorhabditis elegans, rRNAs and some histone mRNAs are heavily targeted by piRNAs, which facilitates their entry into an endogenous RNA interference (RNAi) pathway involving a class of siRNAs called 22G-RNAs. Under normal conditions, rRNAs and histone mRNAs produce relatively low levels of 22G-RNAs. But if piRNAs are lost, 22G-RNA production is highly elevated. We show that 22G-RNAs produced downstream of piRNAs likely function in a feed-forward amplification circuit. Thus, our results suggest that piRNAs facilitate lowlevel 22G-RNA production while simultaneously obstructing the 22G-RNA machinery to prevent runaway amplification from certain RNAs. Histone mRNAs and rRNAs are unique from other cellular RNAs in lacking polyA tails, which may promote feed-forward amplification of 22G-RNAs. In support of this, we show that the subset of histone mRNAs that contain polyA tails are largely resistant to silencing in piRNA mutants.

Computational meta-analysis of ribosomal RNA fragments: potential targets and interaction mechanisms

“…Do sRNAs compete for, or control each other's Ago loading? Age-dependent patterns of Ago loading of miRNAs, tRFs and rRFs in Drosophila ( 16 , 42 , 76 ) or a balance between piRNA and 22-nt rRFs seen in the nematode ( 104 ) suggest such a possibility. Are agotrons targets of sRNA or longer regulatory (and possibly competing) RNAs?…”

Small RNAs in epigenetic inheritance: from mechanisms to trait transmission

“…Similarly, removing some WAGOs downstream of the piRNA pathway contributes to restoring the fertility of piwi mutant worms [ 80 ]. More recent studies have revealed another class of genes that also accumulate 22G‐RNAs in the absence of piRNA, the ribosomal RNA genes [ 81 , 172 ]. However, in the case of the inheritance of 22G‐RNAs antisense to the ribosomal RNAs, called antisense ribosomal siRNAs (risiRNAs), it is not clear whether they interfere with the transcription or the processing of ribosomal RNAs and how they can contribute to the sterility phenotype [ 173 , 174 , 175 ].…”