Year: 2020
Type: article
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.
Source: Cell Reports
Authors: Jonathan J. Ipsaro, Paul A. O’Brien, Shibani Bhattacharya, Arthur G. Palmer, Leemor Joshua-Tor
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: Center on Macromolecular Dynamics by NMR Spectroscopy, Upgrade of 800 MHz Spectrometer, Upgrade of 600 MHz NMR spectrometer, G666505512, Structural Basis for RNA-induced Silencing via the Piwi Clade of Argonautes, Training Program in Molecular Biophysics, NMR Studies of Structure and Dynamic of Proteins, G9000279778, Macromolecular dynamics and conformational changes in biological function, DROSOPHILA GENOMICS RESOURCE CENTER, CSHL Cancer Center Support Grant
OpenAlex ID: W3148607547