Ipsaro, Jonathan J, O’Brien, Paul A, Bhattacharya, Shibani, Palmer, Arthur G, Joshua-Tor, Leemor (August 2020) Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons. BioRxiv. (Unpublished)
Abstract
The piRNA pathway safeguards genomic integrity by silencing transposable elements 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 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. We further show that LTR retrotransposons are preferentially de-repressed in Asterix mutants. Given the role of tRNAs as LTR retrotransposon primers, our work implicates Asterix/Gtsf1 as exploiting tRNA dependence to identify transposon transcripts and promote piRNA silencing.
| Item Type: | Paper |
|---|---|
| Subjects: | 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 > piRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > tRNA |
| CSHL Authors: | |
| Communities: | CSHL labs > Joshua-Tor lab CSHL Cancer Center Program > Gene Regulation and Inheritance Program |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 11 August 2020 |
| Date Deposited: | 13 Jul 2021 18:04 |
| Last Modified: | 13 Jul 2021 18:04 |
| URI: | https://repository.cshl.edu/id/eprint/40280 |
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