henn-1/HEN1 Promotes Germline Immortality in Caenorhabditis elegans

Svendsen, Joshua M.; Reed, Kailee J.; Vijayasarathy, Tarah; Montgomery, Brooke E. E.; Tucci, Rachel M.; Brown, Kristen C.; Marks, Taylor N.; Nguyen, Dieu An H; Phillips, Carolyn M.; Montgomery, Taiowa A.

doi:10.1016/j.celrep.2019.10.114

Cited by 18 publications

(31 citation statements)

References 80 publications

(187 reference statements)

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“…Finally, we show that ZSP-1 contributes to germline immortality. Multiple proteins involved in endo siRNA and piRNA pathways also contribute to germline immortality (Buckley et al, 2012;Simon et al, 2014;Sakaguchi et al, 2014;Svendsen et al, 2019); thus, the defects in germline immortality we see in zsp-1(À) animals are likely connected to the role of ZSP-1 in endo siRNA or piRNA biology. Together, the data lead us to propose that one biological function of the Z granule is to orchestrate and coordinate small RNA-based gene regulation in the germline to ensure the immortal state of the germline.…”

Section: Discussionmentioning

confidence: 95%

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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Section: Discussionmentioning

confidence: 95%

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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“…It is challenging to compare levels of wild-type piRNAs with those in henn-1 mutants because 2′-O-methylation inhibits 3′ adaptor ligation during high-throughput sequencing library preparation as described ( Munafó and Robb, 2010 ; Svendsen et al, 2019 ). To minimize such a bias, we attempted to clone 2′-O-methyl RNA species by adding polyethylene glycol during the adaptor ligation step as described ( Dard-Dascot et al, 2018 ; Munafó and Robb, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

“…Because HENN-1 is required for piRNA accumulation in embryos ( Billi et al, 2012 ; Montgomery et al, 2012 ; Svendsen et al, 2019 ), we next profiled small RNAs from wild-type and mutant early embryos. When analyzing the reads mapping piRNA loci, we found that the abundance of piRNAs in henn-1 and parn-1 mutant embryos was reduced to 87.5% and 60.9%, respectively, as compared to that of the wild type ( Figure S1I ).…”

Section: Resultsmentioning

confidence: 99%

pre-piRNA trimming and 2′-O-methylation protect piRNAs from 3′ tailing and degradation in C. elegans

et al. 2021

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SUMMARY The Piwi-interacting RNA (piRNA) pathway suppresses transposable elements and promotes fertility in diverse organisms. Maturation of piRNAs involves pre-piRNA trimming followed by 2′-O-methylation at their 3′ termini. Here, we report that the 3′ termini of Caenorhabditis elegans piRNAs are subject to nontemplated nucleotide addition, and piRNAs with 3′ addition exhibit extensive base-pairing interaction with their target RNAs. Animals deficient for PARN-1 (pre-piRNA trimmer) and HENN-1 (2′-O-methyltransferase) accumulate piRNAs with 3′ nontemplated nucleotides. In henn-1 mutants, piRNAs are shortened prior to 3′ addition, whereas long isoforms of untrimmed piRNAs are preferentially modified in parn-1 mutant animals. Loss of either PARN-1 or HENN-1 results in modest reduction in steady-state levels of piRNAs. Deletion of both enzymes leads to depletion of piRNAs, desilenced piRNA targets, and impaired fecundity. Together, our findings suggest that pre-piRNA trimming and 2′-O-methylation act collaboratively to protect piRNAs from tailing and degradation.

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“…Reads per million were plotted along the WS258 genome using Integrative Genomics Viewer 2.3.68 ( Robinson et al, 2011 ). ERGO-1 target genes were defined using our ergo-1 libraries, and mutator target genes, piRNA target genes, RDE-1 target genes, and CSR-1 target genes were previously described ( Gu et al, 2009 ; Lee et al, 2012 ; Phillips et al, 2014 ; Svendsen et al, 2019 ; Tsai et al, 2015 ; Zhang et al, 2011 ). Sequencing data is summarized in Table S2 .…”

Section: Methodsmentioning

confidence: 99%

A Small-RNA-Mediated Feedback Loop Maintains Proper Levels of 22G-RNAs in C. elegans

Rogers

Phillips

2020

Cell Reports

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SUMMARY RNA interference (RNAi) is an essential regulatory mechanism in all animals. In Caenorhabditis elegans , several classes of small RNAs act to silence or license expression of mRNA targets. ERI-6/7 is required for the production of some endogenous small interfering RNAs (siRNAs) and acts as a negative regulator of the exogenous RNAi pathway. We find that the genomic locus encoding eri-6/7 contains two distinct regions that are targeted by endogenous siRNAs. Loss of these siRNAs disrupts eri-6/7 mRNA expression, resulting in increased production of siRNAs from other small RNA pathways because these pathways compete with eri-6/7 -dependent transcripts for access to the downstream siRNA amplification machinery. Thus, the pathway acts like a small-RNA-mediated feedback loop to ensure homeostasis of gene expression by small RNA pathways. Similar feedback loops that maintain chromatin homeostasis have been identified in yeast and Drosophila melanogaster , suggesting an evolutionary conservation of feedback mechanisms in gene regulatory pathways.

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henn-1/HEN1 Promotes Germline Immortality in Caenorhabditis elegans

Cited by 18 publications

References 80 publications

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

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

pre-piRNA trimming and 2′-O-methylation protect piRNAs from 3′ tailing and degradation in C. elegans

A Small-RNA-Mediated Feedback Loop Maintains Proper Levels of 22G-RNAs in C. elegans

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