6X46

NMR solution structure of Asterix/Gtsf1 from mouse (CHHC zinc finger domains)

Summary for 6X46

• Entry DOI: 10.2210/pdb6x46/pdb
• NMR Information: BMRB: 30754
• Descriptor: Gametocyte-specific factor 1, ZINC ION (2 entities in total)
• Functional Keywords: chhc zinc finger, rna binding, rna binding protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 14348.42

Authors

Ipsaro, J.J.,O'Brien, P.A.,Bhattacharya, S.,Palmer III, A.G.,Joshua-Tor, L. (deposition date: 2020-05-22, release date: 2021-03-03, Last modification date: 2024-05-01)

Primary citation

Ipsaro, J.J.,O'Brien, P.A.,Bhattacharya, S.,Palmer III, A.G.,Joshua-Tor, L.
Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons.
Cell Rep, 34:108914-108914, 2021

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 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.

PubMed: 33789107
DOI: 10.1016/j.celrep.2021.108914

Experimental method

SOLUTION NMR