A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis

Cell. 2019 Dec 12;179(7):1566-1581.e16. doi: 10.1016/j.cell.2019.11.022.

Abstract

Spermiogenesis is a highly orchestrated developmental process during which chromatin condensation decouples transcription from translation. Spermiogenic mRNAs are transcribed earlier and stored in a translationally inert state until needed for translation; however, it remains largely unclear how such repressed mRNAs become activated during spermiogenesis. We previously reported that the MIWI/piRNA machinery is responsible for mRNA elimination during late spermiogenesis in preparation for spermatozoa production. Here we unexpectedly discover that the same machinery is also responsible for activating translation of a subset of spermiogenic mRNAs to coordinate with morphological transformation into spermatozoa. Such action requires specific base-pairing interactions of piRNAs with target mRNAs in their 3' UTRs, which activates translation through coupling with cis-acting AU-rich elements to nucleate the formation of a MIWI/piRNA/eIF3f/HuR super-complex in a developmental stage-specific manner. These findings reveal a critical role of the piRNA system in translation activation, which we show is functionally required for spermatid development.

Publication types

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

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism*
  • Base Pairing
  • Cells, Cultured
  • ELAV-Like Protein 1 / metabolism
  • Eukaryotic Initiation Factor-3 / metabolism
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptide Chain Initiation, Translational*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Spermatogenesis*

Substances

  • 3' Untranslated Regions
  • Argonaute Proteins
  • ELAV-Like Protein 1
  • Eukaryotic Initiation Factor-3
  • Piwil1 protein, mouse
  • RNA, Messenger
  • RNA, Small Interfering