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TitleAsterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons.
Journal, issue, pagesCell Rep, Vol. 34, Issue 13, Page 108914, Year 2021
Publish dateMar 30, 2021
AuthorsJonathan J Ipsaro / Paul A O'Brien / Shibani Bhattacharya / Arthur G Palmer / Leemor Joshua-Tor /
PubMed AbstractThe 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 ...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.
External linksCell Rep / PubMed:33789107 / PubMed Central
MethodsEM (single particle) / NMR (solution)
Resolution9.8 - 9.9 Å
Structure data

EMDB-22040:
Asterix/Gtsf1 from mouse (full-length protein) bound to co-purifying tRNA
Method: EM (single particle) / Resolution: 9.8 Å

EMDB-22041:
Asterix/Gtsf1 from mouse (residues 1-45; zinc finger 1) bound to co-purifying tRNA
Method: EM (single particle) / Resolution: 9.9 Å

PDB-6x46:
NMR solution structure of Asterix/Gtsf1 from mouse (CHHC zinc finger domains)
Method: SOLUTION NMR

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • mus musculus (house mouse)
  • Spodoptera frugiperda (fall armyworm)
KeywordsRNA BINDING PROTEIN / CHHC zinc finger / RNA binding

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