Developmental roles and molecular mechanisms of Asterix/GTSF1

Ipsaro, Jonathan J.; Joshua‐Tor, Leemor

doi:10.1002/wrna.1716

Cited by 6 publications

(6 citation statements)

References 69 publications

(194 reference statements)

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“…We discover that Paramecium Gtsf1 is a nuclear Ptiwi09-interacting protein in the maternal MAC. The conserved Asterix/Gametocyte-specific factor 1 (GTSF1) proteins are essential piRNA factors that contribute to the repression of transposons in mice, Drosophila and zebrafish (Ipsaro and Joshua-Tor, 2022). We show that Paramecium Gtsf1 is involved in scnRNA-guided TE repression by controlling the degradation of MAC-scnRNAs and of the Ptiwi09 protein.…”

Section: Introductionmentioning

confidence: 99%

The nuclear PIWI-interacting protein Gtsf1 controls the selective degradation of small RNAs inParamecium

Charmant,

Gruchota,

Arnaiz

et al. 2023

Preprint

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Ciliates undergo developmentally programmed genome elimination, in which small RNAs direct the removal of target DNA segments, including transposable elements. At each sexual generation, the development of the macronucleus (MAC) requires massive and reproducible elimination of a large proportion of the germline micronuclear (MIC) genome, leading to a highly streamlined somatic MAC genome. 25-nt long scnRNAs are produced from the entire germline MIC genome during meiosis, and this initial complex small RNA population is then transported to the maternal MAC, where selection of scnRNAs corresponding to germline (MIC)-specific sequences is thought to take place. Selected scnRNAs, loaded onto the PIWI protein Ptiwi09, guide the deposition of histone H3 post-translational modifications (H3K9me3 and H3K27me3) onto transposable elements in the developing macronucleus, ultimately triggering their specific elimination. How germline-specific MIC scnRNAs are selected remains to be determined. Here, we provide important mechanistic insights into the scnRNA selection pathway by identifying aParameciumhomolog of Gametocyte specific factor 1 (Gtsf1) as essential for the selective degradation of scnRNAs corresponding to retained somatic MAC sequences. Consistently, we also show that Gtsf1 is exclusively localized in the maternal macronucleus and associates with the scnRNA-binding protein Ptiwi09. Furthermore, Gtsf1 is necessary for DNA elimination and correct H3K9me3 and H3K27me3 localization in the new developing macronucleus, demonstrating that the scnRNA selection process is important for genome elimination. We propose that Gtsf1 is required for the coordinated degradation of Ptiwi09-scnRNA complexes that pair with nascent RNA transcribed from the maternal MAC genome, similarly to the mechanism suggested for microRNA target-directed degradation in metazoans.

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Section: Introductionmentioning

confidence: 99%

The nuclear PIWI-interacting protein Gtsf1 controls the selective degradation of small RNAs inParamecium

Charmant,

Gruchota,

Arnaiz

et al. 2023

Preprint

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“…Recently, Arif et al ( 2022 ) reported that gametocyte‐specific factor (Gtsf) proteins stimulate the catalytic activity of PIWI proteins. Gtsf proteins act in the piRNA pathway in different species, including flies, silkworms, and mice (Ipsaro & Joshua‐Tor, 2022 ). In Drosophila , Gtsf1 is required for piRNA‐mediated transcriptional gene silencing, but Gtsf1 is not essential for piRNA biogenesis (Dönertas et al , 2013 ; Ohtani et al , 2013 ).…”

Section: Introductionmentioning

confidence: 99%

An extended Tudor domain within Vreteno interconnects Gtsf1L and Ago3 for piRNA biogenesis in Bombyx mori

Bronkhorst,

Lee,

Möckel

et al. 2023

The EMBO Journal

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Piwi‐interacting RNAs (piRNAs) direct PIWI proteins to transposons to silence them, thereby preserving genome integrity and fertility. The piRNA population can be expanded in the ping‐pong amplification loop. Within this process, piRNA‐associated PIWI proteins (piRISC) enter a membraneless organelle called nuage to cleave their target RNA, which is stimulated by Gtsf proteins. The resulting cleavage product gets loaded into an empty PIWI protein to form a new piRISC complex. However, for piRNA amplification to occur, the new RNA substrates, Gtsf‐piRISC, and empty PIWI proteins have to be in physical proximity. In this study, we show that in silkworm cells, the Gtsf1 homolog BmGtsf1L binds to piRNA‐loaded BmAgo3 and localizes to granules positive for BmAgo3 and BmVreteno. Biochemical assays further revealed that conserved residues within the unstructured tail of BmGtsf1L directly interact with BmVreteno. Using a combination of AlphaFold modeling, atomistic molecular dynamics simulations, and in vitro assays, we identified a novel binding interface on the BmVreteno‐eTudor domain, which is required for BmGtsf1L binding. Our study reveals that a single eTudor domain within BmVreteno provides two binding interfaces and thereby interconnects piRNA‐loaded BmAgo3 and BmGtsf1L.

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“…Recently, Arif et al reported that gametocyte-specific factor proteins (Gtsf) stimulate the catalytic activity of PIWI proteins (Arif et al , 2022). Gtsf proteins act in the piRNA pathway in different species, including flies, silkworms and mice (Ipsaro & Joshua-Tor, 2022). In Drosophila , Gtsf1 is required for piRNA-mediated transcriptional gene silencing and is not essential for piRNA biogenesis (Dönertas et al , 2013; Ohtani et al , 2013).…”

Section: Introductionmentioning

confidence: 99%

An extended Tudor domain within Vreteno interconnects Gtsf1L and Ago3 for piRNA biogenesis inBombyx mori

Bronkhorst

Luck

Stelzl

et al. 2023

Preprint

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Piwi-interacting RNAs (piRNAs) direct PIWI proteins to transposons to silence them, thereby preserving genome integrity and fertility. The piRNA population can be expanded in the ping-pong amplification loop. Within this process, piRNA-associated PIWI proteins (piRISC) enter the nuage to cleave target RNA, which is stimulated by Gtsf proteins. The resulting cleavage product gets loaded into an empty PIWI protein to form a new piRISC complex. However, for piRNA amplification to occur, it is required that new RNA substrates, Gtsf-piRISC and empty PIWI proteins are all in physical proximity. In this study we show that BmGtsf1L binds to piRNA-loaded BmAgo3 and co-localizes to BmAgo3-BmVreteno positive granules. Biochemical assays further revealed that conserved residues within the unstructured tail of BmGtsf1L directly interact with BmVreteno. Using a combination of AlphaFold modeling, atomistic molecular dynamics simulations and in vitro assays we identified a novel binding interface on a BmVreteno-eTudor domain, which is required for BmGtsf1L binding. Our study reveals that a single eTudor domain within BmVreteno provides two binding interfaces and thereby interconnects piRNA-loaded BmAgo3 and BmGtsf1L.

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Developmental roles and molecular mechanisms of Asterix/GTSF1

Cited by 6 publications

References 69 publications

The nuclear PIWI-interacting protein Gtsf1 controls the selective degradation of small RNAs inParamecium

The nuclear PIWI-interacting protein Gtsf1 controls the selective degradation of small RNAs inParamecium

An extended Tudor domain within Vreteno interconnects Gtsf1L and Ago3 for piRNA biogenesis in Bombyx mori

An extended Tudor domain within Vreteno interconnects Gtsf1L and Ago3 for piRNA biogenesis inBombyx mori

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