Intrinsically disordered protein PID‐2 modulates Z granules and is required for heritable piRNA‐induced silencing in the<i>Caenorhabditis elegans</i>embryo

Placentino, Maria; Domingues, António Miguel de Jesus; Schreier, Jan; Dietz, Sabrina; Hellmann, Svenja; Albuquerque, Bruno F.M. de; Butter, Falk; Ketting, René F.

doi:10.15252/embj.2020105280

Cited by 16 publications

(43 citation statements)

References 96 publications

(184 reference statements)

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“…Prior to our findings, there were six known Z granule components ( 65 , 79 , 88 ), thus the identification of CSR-1 isoforms in association with ZNFX-1 is important. Although there are some limitations of our analysis to consider, including the facts that we were not able to visualize PGL-1, ZNFX-1, and CSR-1 in the same strains, and that our imaging represents a snapshot (and not live tracking) of development, there are several important implications.…”

Section: Discussionmentioning

confidence: 57%

Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility

Charlesworth

Seroussi

Lehrbach

et al. 2021

Nucleic Acids Research

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The Caenorhabditis elegans genome encodes nineteen functional Argonaute proteins that use 22G-RNAs, 26G-RNAs, miRNAs or piRNAs to regulate target transcripts. Only one Argonaute is essential under normal laboratory conditions: CSR-1. While CSR-1 has been studied widely, nearly all studies have overlooked the fact that the csr-1 locus encodes two isoforms. These isoforms differ by an additional 163 amino acids present in the N-terminus of CSR-1a. Using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG into the long (CSR-1a) and short (CSR-1b) isoforms, we found that CSR-1a is expressed during spermatogenesis and in several somatic tissues, including the intestine. CSR-1b is expressed constitutively in the germline. small RNA sequencing of CSR-1 complexes shows that they interact with partly overlapping sets of 22G-RNAs. Phenotypic analyses reveal that the essential functions of csr-1 described in the literature coincide with CSR-1b, while CSR-1a plays tissue specific functions. During spermatogenesis, CSR-1a integrates into an sRNA regulatory network including ALG-3, ALG-4 and WAGO-10 that is necessary for fertility at 25°C. In the intestine, CSR-1a silences immunity and pathogen-responsive genes, and its loss results in improved survival from the pathogen Pseudomonas aeruginosa. Our findings functionally distinguish the CSR-1 isoforms and highlight the importance of studying each AGO isoform independently.

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Section: Discussionmentioning

confidence: 57%

Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility

Charlesworth

Seroussi

Lehrbach

et al. 2021

Nucleic Acids Research

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“…For reasons described below, we refer to this gene as Z granule surface protein‐1 ( zsp‐1 ). [Note, a related study refers to zsp‐1 as piRNA‐induced silencing defective (pid)‐2 (Placentino et al , 2020). ] We mapped all three class II alleles to the left arm of chromosome I (Fig 2B and Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

“…[Note added in proof. A recent study shows that, indeed, zsp‐1 (also known as pid‐2 ) mutant animals exhibit elevated levels of transposon mobilization in the germline (Placentino et al , 2020)].…”

Section: Discussionmentioning

confidence: 99%

ZSP‐1 is a Z granule surface protein required for Z granule fluidity and germline immortality in Caenorhabditis elegans

et al. 2021

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Germ granules are biomolecular condensates that form in germ cells of all/most animals, where they regulate mRNA expression to promote germ cell function and totipotency. In the adult Caenorhabditis elegans germ cell, these granules are composed of at least four distinct sub-compartments, one of which is the Z granule. To better understand the role of the Z granule in germ cell biology, we conducted a genetic screen for genes specifically required for Z granule assembly or morphology. Here, we show that zsp-1, which encodes a low-complexity/polyampholyte-domain protein, is required for Z granule homeostasis. ZSP-1 localizes to the outer surface of Z granules. In the absence of ZSP-1, Z granules swell to an abnormal size, fail to segregate with germline blastomeres during development, and lose their liquid-like character. Finally, ZSP-1 promotes piRNA-and siRNA-directed gene regulation and germline immortality. Our data suggest that Z granules coordinate small RNA-based gene regulation to promote germ cell function and that ZSP-1 helps/is need to maintain Z granule morphology and liquidity.

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“…PID-2/4/5 are recently identified factors that affect the structure of Z granules, are required for germ cell immortality, and are similarly required to balance 22G-RNA signals. [38,39] These studies demonstrate a link between Z granules and the biogenesis and inheritance of 22G-RNAs.…”

Section: Introductionmentioning

confidence: 71%

“…[36] Known sub-granules include Z-granules, SIMR foci, and Mutator foci -each containing sets of proteins that refine and resolve processes or steps of small RNA biosynthesis. [37][38][39] C. elegans expresses several classes of small RNAs. [40,41] 21U-RNAs are considered the piRNAs of C. elegans due to their interaction with the germline-expressed PRG-1 Argonaute, the main Piwi-class Argonaute of C. elegans.…”

Section: Introductionmentioning

confidence: 99%

The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline

et al. 2021

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LOTUS and Tudor domain containing proteins have critical roles in the germline. Proteins that contain these domains, such as Tejas/Tapas in Drosophila, help localize Vasa to the germ granules and facilitate piRNA-mediated transposon silencing. The homologous proteins in mammals, TDRD5 and TDRD7, are required during spermiogenesis. Until now, proteins containing both LOTUS and Tudor domains in Caenorhabditis elegans have remained elusive. Here we describe LOTR-1 (D1081.7), which derives its name from its LOTUS and Tudor domains. Interestingly, LOTR-1 docks next to P granules to colocalize with the broadly conserved Z-granule helicase, ZNFX-1. LOTR-1's Z-granule association requires its Tudor domain, but both LOTUS and Tudor deletions affect brood size when coupled with a knockdown of the Vasa homolog glh-1. In addition to interacting with the germ-granule components WAGO-1, PRG-1 and DEPS-1, we identified a Tudor-dependent association with ZNFX-1. Like znfx-1 mutants, lotr-1 mutants lose small RNAs from the 3' ends of WAGO and Mutator targets, reminiscent of the loss of piRNAs from the 3' ends of piRNA precursor transcripts in mouse Tdrd5 mutants. Our work suggests that LOTR-1 acts in a conserved mechanism that brings small RNA generating mechanisms towards the 3' ends of small RNA templates or precursors.

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Intrinsically disordered protein PID‐2 modulates Z granules and is required for heritable piRNA‐induced silencing in theCaenorhabditis elegansembryo

Cited by 16 publications

References 96 publications

Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility

Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility

ZSP‐1 is a Z granule surface protein required for Z granule fluidity and germline immortality in Caenorhabditis elegans

The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline

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