| 2022 |
GTSF1 potentiates the weak, intrinsic, piRNA-directed RNA cleavage (endoribonuclease) activities of PIWI-clade Argonaute proteins (MIWI, MILI), transforming them into efficient endoribonucleases; GTSF1 is thus an auxiliary protein that directly enhances the catalytic activity of PIWI Argonautes. |
In vitro RNA cleavage assays with purified components, functional characterization of GTSF1–PIWI interaction |
Nature |
High |
35772669
|
| 2013 |
Drosophila Gtsf1 directly interacts with a small subpool of nuclear PIWI protein and is an essential component of the Piwi-mediated transcriptional silencing complex; cells lacking Gtsf1 contain nuclear Piwi loaded with piRNAs but Piwi's silencing capacity is ablated, and loss of Gtsf1 phenocopies loss of Piwi with respect to transposon derepression and loss of H3K9me3 marks at transposon insertions. |
Genetic loss-of-function (gtsf1 mutant flies), co-immunoprecipitation showing direct Gtsf1–Piwi interaction, chromatin analysis (H3K9me3), transposon expression profiling |
Genes & development |
High |
23913922
|
| 2018 |
Mouse GTSF1 associates with both MILI and MIWI2 PIWI proteins in prospermatogonia; GTSF1 deficiency causes severe defects in secondary piRNA biogenesis because target RNAs of PIWI-piRNAs are left unsliced at the cleavage site, establishing GTSF1 as a crucial factor for PIWI-piRNA-directed target RNA slicing. |
Co-immunoprecipitation of GTSF1 with MILI and MIWI2, analysis of piRNA populations in Gtsf1 mutant mice, mapping of unsliced target RNA cleavage sites |
EMBO reports |
High |
29437694
|
| 2009 |
Mouse GTSF1/Cue110 protein localizes to the cytoplasm of male germ cells; Gtsf1-null males are sterile due to apoptotic death of germ cells after postnatal day 14 and meiotic arrest before the zygotene stage; loss of Gtsf1 causes increased transcription of LINE-1 and IAP retrotransposons accompanied by demethylation of their promoter regions, indicating a role in retrotransposon DNA methylation-dependent silencing in male germ cells. |
Gene targeting (Gtsf1-null mice), immunofluorescence localization, bisulfite sequencing of retrotransposon promoters, RT-PCR of retrotransposon transcripts |
Developmental biology |
High |
19735653
|
| 2021 |
Mouse Gtsf1 specifically binds tRNAs via its first CHHC zinc finger domain; the NMR structure of mouse Gtsf1 identified the RNA-binding interface on the first zinc finger, confirmed by cryo-EM structures of Gtsf1 in complex with co-purifying tRNA and biochemical analysis; LTR retrotransposons (which depend on tRNA primers) are preferentially de-repressed in Asterix/Gtsf1 mutants, linking tRNA binding by Gtsf1 to LTR retrotransposon silencing. |
eCLIP (enhanced crosslinking and immunoprecipitation), NMR spectroscopy (structure determination), cryo-EM structure of Gtsf1–tRNA complex, biochemical binding assays, Asterix mutant transposon analysis |
Cell reports |
High |
33789107
|
| 2018 |
C. elegans GTSF-1 interacts with RRF-3 (an RNA-dependent RNA polymerase) via its CHHC zinc fingers both in vivo and in vitro, and is required for assembly of the larger RRF-3/DCR-1-containing ERIC complex, thereby enabling 26G-RNA biogenesis; notably, in C. elegans GTSF-1 is not required for Piwi-mediated gene silencing but instead functions in a distinct small RNA production complex. |
In vivo and in vitro interaction assays (Co-IP, pulldown), genetic loss-of-function (gtsf-1 mutants), small RNA sequencing, mass spectrometry interactome |
The EMBO journal |
High |
29769402
|
| 2020 |
Bombyx mori GTSF1 (BmGTSF1) physically interacts with BmSIWI (a PIWI-clade Argonaute) and functions as a cofactor of BmSIWI; BmGtsf1 is required for biogenesis of Fem piRNAs that specify female sex determination, and its loss causes piRNA biogenesis defects, transposon derepression, and gametogenesis defects in both sexes. |
Co-immunoprecipitation (BmGTSF1–BmSIWI interaction), CRISPR/Cas9 knockout of BmGtsf1, small RNA sequencing, sex-determination gene expression analysis |
PLoS genetics |
Medium |
33137136
|
| 2024 |
Paramecium tetraurelia GTSF1 (PtGtsf1) interacts with PIWI protein Ptiwi09 and Polycomb Repressive Complex 2 (PRC2); PtGtsf1 is essential for PIWI-dependent DNA elimination of transposons during sexual development and for degradation of self-matching PIWI-bound small RNAs; loss of PtGtsf1 causes accumulation of H3K9me3 and H3K27me3, demonstrating that the PIWI–GTSF1 interaction and its role in transposon silencing are conserved in unicellular eukaryotes. |
Co-immunoprecipitation (PtGtsf1 with Ptiwi09 and PRC2), genetic knockdown/loss-of-function, small RNA sequencing, chromatin modification analysis (H3K9me3, H3K27me3) |
Nucleic acids research |
Medium |
39441077
|
| 2025 |
Paramecium Gtsf1 localizes to the maternal somatic nucleus, associates with the scnRNA-binding protein Ptiwi09, and is required for selective degradation of scnRNAs (scanRNAs) corresponding to retained somatic sequences via the ubiquitin pathway, thereby enabling proper genome elimination during sexual development. |
Localization by imaging, Co-immunoprecipitation (Gtsf1–Ptiwi09), genetic knockdown, small RNA sequencing, ubiquitin pathway analysis |
Nucleic acids research |
Medium |
39571614
|
| 2025 |
Drosophila Tpp (a GTSF1 family PIWI cofactor) mediates abundant piRNA production (particularly Aubergine-bound piRNAs) in nurse cell nuage; loss of tpp reduces piRNA levels, impairs Aubergine localization to the germ plasm, and disrupts germ cell formation, demonstrating that this GTSF1 homolog coordinates piRNA production with germ plasm assembly. |
Genetic loss-of-function (tpp mutant Drosophila), small RNA sequencing, live imaging of Aubergine localization, germ cell counting |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
40493187
|
| 2025 |
In bladder cancer cells, GTSF1 forms a complex with PIWIL4 that, when guided by piR-43452 bound to the 3'UTR of LRP1 mRNA, enhances target RNA cleavage through GTSF1-dependent conformational activation of PIWIL4, leading to LRP1 mRNA destabilization. |
Co-immunoprecipitation (GTSF1–PIWIL4 complex), RNA binding assays (piR-43452 to LRP1 3'UTR), in vitro and in vivo functional assays (siRNA knockdown, xenograft) |
Translational oncology |
Low |
41344056
|