Coupled protein synthesis and ribosome-guided piRNA processing on mRNAs

Nat Commun. 2021 Oct 13;12(1):5970. doi: 10.1038/s41467-021-26233-8.

Abstract

PIWI-interacting small RNAs (piRNAs) protect the germline genome and are essential for fertility. piRNAs originate from transposable element (TE) RNAs, long non-coding RNAs, or 3´ untranslated regions (3´UTRs) of protein-coding messenger genes, with the last being the least characterized of the three piRNA classes. Here, we demonstrate that the precursors of 3´UTR piRNAs are full-length mRNAs and that post-termination 80S ribosomes guide piRNA production on 3´UTRs in mice and chickens. At the pachytene stage, when other co-translational RNA surveillance pathways are sequestered, piRNA biogenesis degrades mRNAs right after pioneer rounds of translation and fine-tunes protein production from mRNAs. Although 3´UTR piRNA precursor mRNAs code for distinct proteins in mice and chickens, they all harbor embedded TEs and produce piRNAs that cleave TEs. Altogether, we discover a function of the piRNA pathway in fine-tuning protein production and reveal a conserved piRNA biogenesis mechanism that recognizes translating RNAs in amniotes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions*
  • Animals
  • Base Sequence
  • Chickens
  • DNA Transposable Elements
  • Fertility / genetics*
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pachytene Stage
  • Protein Biosynthesis*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Ribosomes / genetics*
  • Ribosomes / metabolism
  • Spermatogenesis / genetics*
  • Testis / cytology
  • Testis / growth & development
  • Testis / metabolism

Substances

  • 3' Untranslated Regions
  • DNA Transposable Elements
  • RNA, Small Interfering