Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons

Cell Rep. 2021 Mar 30;34(13):108914. doi: 10.1016/j.celrep.2021.108914.


The Piwi-interacting RNA (piRNA) pathway safeguards genomic integrity by silencing transposable elements (transposons) in the germline. While Piwi is the central piRNA factor, others including Asterix/Gtsf1 have also been demonstrated to be critical for effective silencing. Here, using enhanced crosslinking and immunoprecipitation (eCLIP) with a custom informatic pipeline, we show that Asterix/Gtsf1 specifically binds tRNAs in cellular contexts. We determined the structure of mouse Gtsf1 by NMR spectroscopy and identified the RNA-binding interface on the protein's first zinc finger, which was corroborated by biochemical analysis as well as cryo-EM structures of Gtsf1 in complex with co-purifying tRNA. Consistent with the known dependence of long terminal repeat (LTR) retrotransposons on tRNA primers, we demonstrate that LTR retrotransposons are, in fact, preferentially de-repressed in Asterix mutants. Together, these findings link Asterix/Gtsf1, tRNAs, and LTR retrotransposon silencing and suggest that Asterix exploits tRNA dependence to identify transposon transcripts and promote piRNA silencing.

Keywords: Asterix; Gtsf1; LTR; NMR; RNA; cryoEM; eCLIP; piRNA; retrotransposon; tRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Gene Silencing*
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA, Small Interfering / metabolism*
  • RNA, Transfer / chemistry
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism*
  • Recombinant Proteins / biosynthesis
  • Retroelements / genetics*
  • Terminal Repeat Sequences


  • Cue110 protein, mouse
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • Retroelements
  • arx protein, Drosophila
  • RNA, Transfer