Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis

Singh, Meetali; Cornes, Eric; Li, Blaise; Quarato, Piergiuseppe; Bourdon, Loan; Dingli, Florent; Loew, Damarys; Proccacia, Simone; Cecere, Germano

doi:10.1038/s41467-021-23615-w

Cited by 27 publications

(37 citation statements)

References 94 publications

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“…Colored boxes represent coding sequences, and gray boxes correspond to non-coding sequences (introns, UTRs). (D) RNA immunoprecipitation (RIP) experiments followed by RT-qPCR showing the log 10 percentage of input for a known CSR-1 target ( csr-1 ) ( Singh et al., 2021 ), and two spermatogenic piRNA targets (ZK795.2 and Y80D3A.8) from λN::CSR-1 and λN::Cherry IPs at the indicated genetic backgrounds. act-3 was used as a non-specific target gene.…”

Section: Resultsmentioning

confidence: 99%

piRNAs initiate transcriptional silencing of spermatogenic genes during C. elegans germline development

et al. 2022

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Summary Eukaryotic genomes harbor invading transposable elements that are silenced by PIWI-interacting RNAs (piRNAs) to maintain genome integrity in animal germ cells. However, whether piRNAs also regulate endogenous gene expression programs remains unclear. Here, we show that C. elegans piRNAs trigger the transcriptional silencing of hundreds of spermatogenic genes during spermatogenesis, promoting sperm differentiation and function. This silencing signal requires piRNA-dependent small RNA biogenesis and loading into downstream nuclear effectors, which correlates with the dynamic reorganization of two distinct perinuclear biomolecular condensates present in germ cells. In addition, the silencing capacity of piRNAs is temporally counteracted by the Argonaute CSR-1, which targets and licenses spermatogenic gene transcription. The spatial and temporal overlap between these opposing small RNA pathways contributes to setting up the timing of the spermatogenic differentiation program. Thus, our work identifies a prominent role for piRNAs as direct regulators of endogenous transcriptional programs during germline development and gamete differentiation.

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Section: Resultsmentioning

confidence: 99%

piRNAs initiate transcriptional silencing of spermatogenic genes during C. elegans germline development

et al. 2022

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“…The decrease in AsCSR-1 levels during the later stages of spermatogenesis may lead to loss of licensing or protection from repression also resulting in a decrease in AsCSR-1 target RNAs. AsCSR-1 could also play a repressive role as recently described [25,95].…”

Section: Discussionmentioning

confidence: 71%

“…C. elegans CSR-1 has also been proposed to "fine tune" gene expression of mRNAs loaded into oocytes [91], clear maternal mRNAs [25], and degrade mRNAs with non-optimal codons [95]. AsCSR-1 is present in oocytes and at its highest level during the maternal to zygotic transition which initiates at the one-cell stage in Ascaris prior to pronuclear fusion [61].…”

Section: Discussionmentioning

confidence: 99%

“…Overall, with no Ascaris piRNAs and 26G-RNAs not likely serving as primary siRNAs to initiate secondary siRNA generation, the origin of endogenous primary siRNAs in Ascaris that lead to the abundant 22G-RNAs is unclear. Recent data suggest that in some C. elegans stages or compartments the CSR-1 slicer activity [22] may initially function to target and cleave mRNAs thereby serving to identify RNAs for RdRPs to initiate the generation of secondary siRNAs for CSR-1 [95].…”

Section: Plasticity Of Ascaris Wago-3 and Nrde-3 Targets Ascaris Wago-1 And Wago-2 Associated Smallmentioning

confidence: 99%

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Nematode Small RNA Pathways in the Absence of piRNAs

Zagoskin

Wang

Neff

et al. 2021

Preprint

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Small RNA pathways play diverse regulatory roles in the nematode C. elegans. However, our understanding of small RNA pathways, their conservation, and their roles in other nematodes is limited. Here, we analyzed small RNA pathways in the parasitic nematode Ascaris. Ascaris has ten Argonautes with five worm-specific Argonautes (WAGOs) that are associated with secondary 5'-triphosphate small RNAs (22-24G-RNAs). These Ascaris WAGOs and their small RNAs target repetitive sequences (WAGO-1, WAGO-2, WAGO-3, and NRDE-3) or mature mRNAs (CSR-1, NRDE-3, and WAGO-3) and are similar to the C. elegans mutator, nuclear, and CSR-1 small RNA pathways. Ascaris CSR-1 likely functions to "license" gene expression in the absence of an Ascaris piRNA pathway. Ascaris ALG-4 and its associated 26G-RNAs target and appear to repress specific mRNAs during meiosis in the testes. Notably, Ascaris WAGOs (WAGO-3 and NRDE-3) small RNAs change their targets between repetitive sequences and mRNAs during spermatogenesis or in early embryos illustrating target plasticity of these WAGOs. We provide a unique and comprehensive view of mRNA and small RNA expression throughout nematode spermatogenesis that illustrates the dynamics and flexibility of small RNA pathways. Overall, our study provides key insights into the conservation and divergence of nematode small RNA pathways.

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“…Here we describe the specific steps for producing GRO-seq libraries from Caenorhabditis elegans worms and embryos. We have used this protocol to generate GRO-seq libraries from as low as 1,000 worms or 40,000 embryos ( Barucci et al, 2020 ; Quarato et al, 2021 ; Singh et al, 2021 ).…”

Section: Before You Beginmentioning

confidence: 99%

Global Run-On sequencing to measure nascent transcription in C. elegans

Quarato

Cecere

2021

STAR Protocols

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Summary Global Run-On sequencing (GRO-seq) is one of the most sensitive techniques to detect nascent transcription from RNA polymerase (Pol) at a genome-wide level. The protocol incorporates labeled ribonucleotides into nascent RNAs from Pol I, II, and III. We have adapted the GRO-seq protocol to the nematode Caenorhabditis elegans to measure transcription from embryos and adult worms. Here, we provide a detailed overview of the protocol highlighting the critical steps for generating successful libraries. For complete details on the use and execution of this protocol, please refer to Quarato et al. (2021) .

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Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis

Cited by 27 publications

References 94 publications

piRNAs initiate transcriptional silencing of spermatogenic genes during C. elegans germline development

piRNAs initiate transcriptional silencing of spermatogenic genes during C. elegans germline development

Nematode Small RNA Pathways in the Absence of piRNAs

Global Run-On sequencing to measure nascent transcription in C. elegans

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