Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons.

Ipsaro, Jonathan J, O'Brien, Paul A, Bhattacharya, Shibani, Palmer, Arthur G, Joshua-Tor, Leemor (March 2021) Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons. Cell Reports, 34 (13). p. 108914. ISSN 2211-1247

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2021.Ipsaro.RetrotransposonSilencing.pdf

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URL: https://www.ncbi.nlm.nih.gov/pubmed/33789107
DOI: 10.1016/j.celrep.2021.108914

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 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.

Item Type: Paper
Subjects: Investigative techniques and equipment > microscopy > Cryo-electron microscopy
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression > transposable elements
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > zinc finger proteins
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 30 March 2021
Date Deposited: 28 Apr 2021 19:47
Last Modified: 19 Jul 2021 13:07
PMCID: PMC8283736
URI: https://repository.cshl.edu/id/eprint/39949

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