Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants

Barucci, Giorgia; Cornes, Eric; Singh, Meetali; Li, Blaise; Ugolini, Martino; Samolygo, Aleksei; Didier, Céline; Dingli, Florent; Loew, Damarys; Quarato, Piergiuseppe; Cecere, Germano

doi:10.1038/s41556-020-0462-7

Cited by 67 publications

(162 citation statements)

References 70 publications

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“…To precisely study the localization of CSR-1 during embryogenesis and in animal development, we have generated different CRISPR-Cas9 tagged versions of CSR-1 (22). As previously observed (23), CSR-1 is expressed mainly in the germline of adult worms and localizes in the cytoplasm and germ granules ( Fig.…”

mentioning

confidence: 81%

“…CRISPR-Cas9 alleles were generated as described previously (22). We used a mCherry::3×Flag::ha::csr-1 (22) as an entry strain to introduce an auxin-inducible Degron tag and obtain a Degron::mCherry::3xFlag::ha::csr-1 strain suitable for the auxin inducible degradation of CSR-1, after crossing with CA1352, a strain carrying a single copy of the germline expressed TIR-1 protein (26).…”

Section: Generation Of Crispr-cas9 Linesmentioning

confidence: 99%

“…Total RNA from staged embryo preparations with RIN>9 was used to generate sRNA libraries as previously described (22). extraction was performed following the manufacturer's instructions.…”

Section: Srna-seq Library Preparationmentioning

confidence: 99%

“…Analysis for RNA-seq, sRNA-seq, and GRO-seq have been performed as previously described (22). Metaprofiles were generated using RPM from sRNA-seq analysis by summarizing normalized coverage information (taken from bigwig files and averaged across replicates) along early degraded targets or late degraded targets using deeptools (40).…”

Section: Sequencing Data Analysesmentioning

confidence: 99%

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Germline inherited small RNAs clear untranslated maternal mRNAs inC. elegansembryos

Quarato

Singh

Cornes

et al. 2020

Preprint

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Argonaute proteins and their interacting small RNAs play a key role in regulating complementary mRNA targets during animal development. Here, we investigate a novel and essential function of the catalytically active Argonaute protein CSR-1 in maternal mRNA degradation during early embryogenesis in Caenorhabditis elegans. We show that CSR-1 interacts with endogenous small RNAs antisense to hundreds of cleared maternal mRNAs in embryos, and preferentially cleaves mRNAs no longer engaged in translation. The depletion of CSR-1 during maternal to zygotic transition leads to embryonic lethality in a catalytic-dependent manner and impairs the degradations of its embryonic mRNA targets. Given the conservation of Argonaute catalytic activity, we propose that a similar mechanism operate to clear maternal mRNAs during maternal to zygotic transition across species. Main Text:The beginning of life in animals is characterized by the transition between maternally supplied factors and the activation of the zygotic genome. The elimination of germline-produced mRNAs and proteins in somatic blastomeres and the concomitant activation of the zygotic genome during early embryonic development, is a critical step to obtain totipotent embryos (1). Several factors that participate in maternal mRNA clearance have been identified, including maternallyinherited PIWI-interacting RNAs (piRNAs) and zygotically-transcribed micro RNAs (miRNAs)(2-6), and features encoded into the mRNA sequence, such as codon optimality (7,8)

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mentioning

confidence: 81%

Section: Generation Of Crispr-cas9 Linesmentioning

confidence: 99%

“…Total RNA from staged embryo preparations with RIN>9 was used to generate sRNA libraries as previously described (22). extraction was performed following the manufacturer's instructions.…”

Section: Srna-seq Library Preparationmentioning

confidence: 99%

Section: Sequencing Data Analysesmentioning

confidence: 99%

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Germline inherited small RNAs clear untranslated maternal mRNAs inC. elegansembryos

Quarato

Singh

Cornes

et al. 2020

Preprint

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“…For example, we and others showed that piRNAs prevent silencing of essential genes by an endogenous RNAi pathway involving small interfering RNAs (siRNAs) (5,6). Recently, the germline mortality of piRNA mutants was linked specifically to the silencing of essential histone genes (7).…”

Section: Introductionmentioning

confidence: 99%

piRNAs prevent runaway amplification of siRNAs from ribosomal RNAs and histone mRNAs

Montgomery

Vijayasarathy

Marks

et al. 2020

Preprint

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Piwi-interacting RNAs (piRNAs) are a largely germline-specific class of small RNAs found in animals.Although piRNAs are best known for silencing transposons, they regulate many different biological processes. Here we identify a role for piRNAs in preventing runaway amplification of small interfering RNAs (siRNAs) from certain genes, including ribosomal RNAs (rRNAs) and histone mRNAs. In Caenorhabditis elegans, rRNAs and some histone mRNAs are heavily targeted by piRNAs, which facilitates their entry into an endogenous RNA interference (RNAi) pathway involving a class of siRNAs called 22G-RNAs. Under normal conditions, rRNAs and histone mRNAs produce relatively low levels of 22G-RNAs. But if piRNAs are lost, 22G-RNA production is highly elevated. We show that 22G-RNAs produced downstream of piRNAs likely function in a feed-forward amplification circuit. Thus, our results suggest that piRNAs facilitate lowlevel 22G-RNA production while simultaneously obstructing the 22G-RNA machinery to prevent runaway amplification from certain RNAs. Histone mRNAs and rRNAs are unique from other cellular RNAs in lacking polyA tails, which may promote feed-forward amplification of 22G-RNAs. In support of this, we show that the subset of histone mRNAs that contain polyA tails are largely resistant to silencing in piRNA mutants.

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Small RNAs in epigenetic inheritance: from mechanisms to trait transmission

Cecere

2021

FEBS Letters

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Inherited information is transmitted to progeny primarily by the genome through the gametes. However, in recent years, epigenetic inheritance has been demonstrated in several organisms, including animals. Although it is clear that certain post-translational histone modifications, DNA methylation, and noncoding RNAs regulate epigenetic inheritance, the molecular mechanisms responsible for epigenetic inheritance are incompletely understood. This review focuses on the role of small RNAs in transmitting epigenetic information across generations in animals. Examples of documented cases of transgenerational epigenetic inheritance are discussed, from the silencing of transgenes to the inheritance of complex traits, such as fertility, stress responses, infections, and behavior. Experimental evidence supporting the idea that small RNAs are epigenetic molecules capable of transmitting traits across generations is highlighted, focusing on the mechanisms by which small RNAs achieve such a function. Just as the role of small RNAs in epigenetic processes is redefining the concept of inheritance, so too our understanding of the molecular pathways and mechanisms that govern epigenetic inheritance in animals is radically changing.

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Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants

Cited by 67 publications

References 70 publications

Germline inherited small RNAs clear untranslated maternal mRNAs inC. elegansembryos

Germline inherited small RNAs clear untranslated maternal mRNAs inC. elegansembryos

piRNAs prevent runaway amplification of siRNAs from ribosomal RNAs and histone mRNAs

Small RNAs in epigenetic inheritance: from mechanisms to trait transmission

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