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| Title | Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons. |
|---|---|
| Journal, issue, pages | Cell Rep, Vol. 34, Issue 13, Page 108914, Year 2021 |
| Publish date | Mar 30, 2021 |
 Authors | Jonathan J Ipsaro / Paul A O'Brien / Shibani Bhattacharya / Arthur G Palmer / Leemor Joshua-Tor /  |
| PubMed Abstract | 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 ...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 links | Cell Rep / PubMed:33789107 / PubMed Central |
| Methods | EM (single particle) / NMR (solution) |
| Resolution | 9.8 - 9.9 Å |
| Structure data |  EMDB-22040:  EMDB-22041:  PDB-6x46: |
| Chemicals |  ChemComp-ZN: |
| Source |
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 Keywords |  RNA BINDING PROTEIN / CHHC zinc finger / RNA binding |
