6x46

Publication Abstract from PubMed

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.

Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons.,Ipsaro JJ, O'Brien PA, Bhattacharya S, Palmer AG 3rd, Joshua-Tor L Cell Rep. 2021 Mar 30;34(13):108914. doi: 10.1016/j.celrep.2021.108914. PMID:33789107^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.