A cytoplasmic Argonaute protein promotes the inheritance of RNAi

Xu, Fei; Feng, Xuezhu; Chen, Xiangyang; Weng, Chenchun; Qi, Yan; Xu, Ting; Hong, Minjie; Guang, Shouhong

doi:10.1101/235713

Cited by 21 publications

(57 citation statements)

References 51 publications

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“…We did not observe strengthening of the heritable responses when comparing pgl-1 to wild type ( Figure S3). The Z granule argonaute WAGO-4 was shown to be required for inheritance of dsRNA-derived exogenous siRNAs 20,21 . Our results show that WAGO-4 is indeed required for RNAi inheritance, but only for initiation of the RNAi response, in the parents which are directly exposed to dsRNA.…”

Section: Resultsmentioning

confidence: 99%

“…Germ granules were hypothesized to balance the levels of different small RNA species 21,22 , and it is well established that different small RNA pathways compete over limited biogenesis factors 7,8,[42][43][44] . To understand how germ granules regulate small RNA levels, we sequenced small RNAs from dissected germlines of germ granule-defective pptr-1 mutants (the mutants that we found to always exhibit strong RNAi inheritance).…”

Section: Resultsmentioning

confidence: 99%

“…Specifically, we found a disruption in endo-siRNAs that bind the nuclear argonaute HRDE-1 (fold enrichment of 6.2x and 3.4x for downregulated, and upregulated small RNAs in pptr-1 mutants, p<10 -4 , Figure 4E). Small RNAs that depend on or bind to proteins localized to germ granules were also substantially disturbed, such as endo-siRNAs associated with P granule proteins (the EGO-1 RdRP 45 , the WAGO-1 19 and the PRG-1 46 argonautes), the M granule protein MUT-16 47 , and the Z granule argonaute WAGO-4 21 (Figure 4E).…”

Section: Resultsmentioning

confidence: 99%

“…Many of the factors which participate in transgenerational small RNA inheritance reside in germline-specific ribonucleoprotein complexes termed germ granules [17][18][19][20][21][22][23] . P granules are RNA-rich, cytoplasmic, perinuclear liquid-like condensates 24 , which are maternally deposited to the oocyte 25,26 , and following fertilization are asymmetrically segregated to the P lineage designated to become the germline 27 .…”

Section: Introductionmentioning

confidence: 99%

“…The Z granules co-localize with P granules, but during the mitotic stage in the adult germline the two granules separate, while remaining adjacent to each other 20 . Z granules contain the WAGO-4 argonaute 20,21 , and the ZNFX-1 protein 20,22 , needed for balanced small RNA amplification 22 . Both proteins were shown to be required for RNAi inheritance [20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

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Germ Granules Functions are Memorized by Transgenerationally Inherited Small RNAs

Lev

Toker

et al. 2019

Preprint

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In C. elegans nematodes, components of liquid-like germ granules were shown to be required for transgenerational small RNA inheritance. Surprisingly, we show here that mutants with defective germ granules (pptr-1, meg-3/4, pgl-1) can nevertheless inherit potent small RNA-based silencing responses, but some of the mutants lose this ability after many generations of homozygosity. Animals mutated in pptr-1, which is required for stabilization of P granules in the early embryo, display extremely strong heritable RNAi responses, which last for tens of generations, long after the responses in wild type animals peter out. The phenotype of mutants defective in the core germ granules proteins MEG-3 and MEG-4, depends on the genotype of the ancestors: Mutants that derive from maternal lineages that had functional MEG-3 and MEG-4 proteins exhibit enhanced RNAi inheritance for multiple generations. While functional ancestral meg-3/4 alleles correct, and even potentiates the ability of mutant descendants to inherit RNAi, defects in germ granules functions can be memorized as well; Wild type descendants that derive from lineages of mutants show impaired RNAi inheritance for many (>16) generations, although their germ granules are intact. Importantly, while P granules are maternally deposited, wild type progeny derived from meg-3/4 male mutants also show reduced RNAi inheritance. Unlike germ granules, small RNAs are inherited also from the sperm.Moreover, we find that the transgenerational effects that depend on the ancestral germ granules require the argonaute protein HRDE-1, which carries heritable small RNAs in the germline. Indeed, small RNA sequencing reveals imbalanced levels of many endogenous small RNAs in germ granules mutants. Strikingly, we find that hrde-1;meg-3/4 triple mutants inherit RNAi, although hrde-1 was previously thought to be essential for heritable silencing. We propose that germ granules sort and shape the RNA pool, and that small RNA inheritance memorizes this activity for multiple generations.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Germ Granules Functions are Memorized by Transgenerationally Inherited Small RNAs

Lev

Toker

et al. 2019

Preprint

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Functions and mechanisms of RNA tailing by metazoan terminal nucleotidyltransferases

Liudkovska

Dziembowski

2020

WIREs RNA

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Termini often determine the fate of RNA molecules. In recent years, 3′ ends of almost all classes of RNA species have been shown to acquire nontemplated nucleotides that are added by terminal nucleotidyltransferases (TENTs). The best‐described role of 3′ tailing is the bulk polyadenylation of messenger RNAs in the cell nucleus that is catalyzed by canonical poly(A) polymerases (PAPs). However, many other enzymes that add adenosines, uridines, or even more complex combinations of nucleotides have recently been described. This review focuses on metazoan TENTs, which are either noncanonical PAPs or terminal uridylyltransferases with varying processivity. These enzymes regulate RNA stability and RNA functions and are crucial in early development, gamete production, and somatic tissues. TENTs regulate gene expression at the posttranscriptional level, participate in the maturation of many transcripts, and protect cells against viral invasion and the transposition of repetitive sequences. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition RNA Processing > 3′ End Processing RNA Turnover and Surveillance > Regulation of RNA Stability

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henn-1/HEN1 Promotes Germline Immortality in Caenorhabditis elegans

et al. 2019

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SUMMARY The germline contains an immortal cell lineage that ensures the faithful transmission of genetic and, in some instances, epigenetic information from one generation to the next. Here, we show that in Caenorhabditis elegans, the small RNA 3′-2′-O-methyltransferase henn-1/HEN1 is required for sustained fertility across generations. In the absence of henn-1, animals become progressively less fertile, becoming sterile after ~30 generations at 25°C. Sterility in henn-1 mutants is accompanied by severe defects in germline proliferation and maintenance. The requirement for henn-1 in transgenerational fertility is likely due to its role in methylating and, thereby, stabilizing Piwi-interacting RNAs (piRNAs). However, despite being essential for piRNA stability in embryos, henn-1 is not required for piRNA stability in adults. Thus, we propose that methylation is important for the role of piRNAs in establishing proper gene silencing during early stages of development but is dispensable for their role in the proliferated germline.

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A cytoplasmic Argonaute protein promotes the inheritance of RNAi

Cited by 21 publications

References 51 publications

Germ Granules Functions are Memorized by Transgenerationally Inherited Small RNAs

Germ Granules Functions are Memorized by Transgenerationally Inherited Small RNAs

Functions and mechanisms of RNA tailing by metazoan terminal nucleotidyltransferases

henn-1/HEN1 Promotes Germline Immortality in Caenorhabditis elegans

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