C. elegans Dicer interacts with the P-granule component GLH-1 and both regulate germline RNPs

Beshore, Erica L.; McEwen, Tamara J.; Jud, Molly C.; Marshall, J.; Schisa, Jennifer A; Bennett, Karen

doi:10.1016/j.ydbio.2010.12.005

Cited by 43 publications

(50 citation statements)

References 72 publications

(96 reference statements)

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“…Third, many passively bound mRNAs encode RNA-granule-associated genes, and we show that Dicer protein itself is granularly localized in the C. elegans germline. Taken together with the observation that Dicer is required for RNP granule formation ( Figure S5D and Beshore et al, 2011), this indicates that passive binding may be important for RNA localization and assembly of RNA-protein complexes. This finding could explain the diverse although overall weak effects observed upon DICER1 knockdown in HEK293 cells and suggests that germ cells, forming prominent RNP structures, are a more suitable system to investigate this aspect of Dicer biology.…”

Section: Discussionsupporting

confidence: 72%

“…The association of passive Dicer binding with RNA granules suggests a role in mRNA localization. Indeed, our FLAG-tagged DCR-1 protein recapitulates the granular localization of wild-type DCR-1 in the C. elegans germline ( Figures 5K and S5E and Beshore et al, 2011).…”

Section: Passive Sites Can Interfere With Catalytic Dicer Activitymentioning

confidence: 68%

“…A hallmark of animal germ cells are RNA granules, perinuclear aggregates of RNA and protein. In C. elegans, Dicer is present in and required for assembly of these granules ( Figure S5D and Beshore et al, 2011). As Dicer is a large protein with many protein interactors and passive binding to mRNAs does not involve RNase activity, we hypothesized that Dicer may additionally play a role in aggregating bound mRNAs to RNA granules.…”

Section: Passive Sites Can Interfere With Catalytic Dicer Activitymentioning

confidence: 99%

“…In human cells, Dicer is present in the nucleus (Doyle et al, 2013;Sinkkonen et al, 2010) and interacts with nuclear pore complexes (Ando et al, 2011). In C. elegans, Dicer localizes to germline P granules and is required for their formation (Beshore et al, 2011). Dicer is also present in chromatoid bodies of mammalian germ cells (Kotaja et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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A Variety of Dicer Substrates in Human and C. elegans

Rybak-Wolf

Jens

Murakawa

et al. 2014

Cell

106

140

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The endoribonuclease Dicer is known for its central role in the biogenesis of eukaryotic small RNAs/microRNAs. Despite its importance, Dicer target transcripts have not been directly mapped. Here, we apply biochemical methods to human cells and C. elegans and identify thousands of Dicer-binding sites. We find known and hundreds of additional miRNAs with high sensitivity and specificity. We also report structural RNAs, promoter RNAs, and mitochondrial transcripts as Dicer targets. Interestingly, most Dicer-binding sites reside on mRNAs/lncRNAs and are not significantly processed into small RNAs. These passive sites typically harbor small, Dicer-bound hairpins within intact transcripts and generally stabilize target expression. We show that passive sites can sequester Dicer and reduce microRNA expression. mRNAs with passive sites were in human and worm significantly associated with processing-body/granule function. Together, we provide the first transcriptome-wide map of Dicer targets and suggest conserved binding modes and functions outside of the miRNA pathway.

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Section: Discussionsupporting

confidence: 72%

Section: Passive Sites Can Interfere With Catalytic Dicer Activitymentioning

confidence: 68%

Section: Passive Sites Can Interfere With Catalytic Dicer Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Variety of Dicer Substrates in Human and C. elegans

Rybak-Wolf

Jens

Murakawa

et al. 2014

Cell

106

140

View full text Add to dashboard Cite

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“…Some reports have suggested that it is as a component of germline perinuclear P--granule structures which are sites of mRNA export and possibly degradation (KAWASAKI et al 1998;SHETH et al 2010), and others have shown that these P--granules' structure or stability depends, at least indirectly, on RNAi components including CSR--1, EGO--1, DCR--1, DRH--3, PRG--1, and RDE--4 (BESHORE et al 2011;CLAYCOMB et al 2009;SPIKE et al 2008; UPDIKE and STROME 2009). While PGL--1's link to RNAs is genetically and biochemically well--established (HANAZAWA et al 2011;SCHISA et al 2001), especially for those in the germline, there are conflicting reports on its role in RNAi.…”

Section: Pgl--1's Link To Rnaimentioning

confidence: 99%

The Nuclear Argonaute NRDE-3 Contributes to Transitive RNAi inCaenorhabditis elegans

Zhuang

Banse²,

Hunter

2013

Genetics

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The Caenorhabditis elegans nuclear RNA interference defective (Nrde) mutants were identified by their inability to silence polycistronic transcripts in enhanced RNAi (Eri) mutant backgrounds. Here, we report additional nrde-3-dependent RNAi phenomena that extend the mechanisms, roles, and functions of nuclear RNAi. We show that nrde-3 mutants are broadly RNAi deficient and that overexpressing NRDE-3 enhances RNAi. Consistent with NRDE-3 being a dose-dependent limiting resource for effective RNAi, we find that NRDE-3 is required for eri-dependent enhanced RNAi phenotypes, although only for a subset of target genes. We then identify pgl-1 as an additional limiting RNAi resource important for eri-dependent silencing of a nonoverlapping subset of target genes, so that an nrde-3; pgl-1; eri-1 triple mutant fails to show enhanced RNAi for any tested gene. These results suggest that nrde-3 and pgl-1 define separate and independent limiting RNAi resource pathways. Limiting RNAi resources are proposed to primarily act via endogenous RNA silencing pathways. Consistent with this, we find that nrde-3 mutants misexpress genes regulated by endogenous siRNAs and incompletely silence repetitive transgene arrays. Finally, we find that nrde-3 contributes to transitive RNAi, whereby amplified silencing triggers act in trans to silence sequence-similar genes. Because nrde-dependent silencing is thought to act in cis to limit the production of primary transcripts, this result reveals an unexpected role for nuclear processes in RNAi silencing. GENETIC analysis of RNA interference (RNAi) in Caenorhabditis elegans initially identified and characterized genes and activities important for post-transcriptional gene silencing (PTGS) in response to exogenous double-stranded RNA (dsRNA) (Tabara et al. 1999(Tabara et al. , 2002. Because these gene products target mature RNAs (mRNAs), they were presumed to act in the cytoplasm . However, a genetic screen for mutants specifically defective for pan-operon RNAi silencing (Bosher et al. 1999) identified genes important for transcriptional gene silencing (TGS) processes that operate in the nucleus (Guang et al. 2008(Guang et al. , 2010Burkhart et al. 2011;Burton et al. 2011). These genes were termed nuclear RNAi defective (nrde).The best-characterized nrde is NRDE-3, an Argonaute that shuttles secondary short-interfering RNAs (siRNAs) from the cytoplasm to the nucleus (Guang et al. 2008). When siRNA are absent or reduced, NRDE-3 is primarily detected in the cytoplasm, and when siRNAs are abundant, NRDE-3 is readily detected in the nucleus. In the nucleus, the siRNAbound NRDE-3 forms a complex with the nuclear restricted NRDE-1, -2, and -4 (Burton et al. 2011). The associated siRNA guides the NRDE complex to cognate nascent mRNA transcripts, which impedes RNA polymerase II transcription elongation and further initiates histone methylation-dependent TGS (Guang et al. 2010;Burton et al. 2011). This RNA-directed epigenetic mechanism also enables multigenerational silencing ; the recently ident...

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Germ granules and the control of mRNA translation

Sengupta

Boag

2012

IUBMB Life

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SummaryGerm granules are an evolutionarily conserved feature of germ cell cytoplasm and are critical for gametogenesis and embryonic development. Germ granules are highly enriched for RNA and RNA-binding proteins and are key centers for posttranscriptional gene regulation in germ cells. Over the last 20 years, the molecular events in germ granule function and formation in several organisms have begun to be revealed. This review seeks to give an overview of some conserved features of germ granules and highlights a conserved strategy for regulating translation of maternal mRNAs. IUBMBIUBMB Life, 64 (7): [586][587][588][589][590][591][592][593][594] 2012

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C. elegans Dicer interacts with the P-granule component GLH-1 and both regulate germline RNPs

Cited by 43 publications

References 72 publications

A Variety of Dicer Substrates in Human and C. elegans

A Variety of Dicer Substrates in Human and C. elegans

The Nuclear Argonaute NRDE-3 Contributes to Transitive RNAi inCaenorhabditis elegans

Germ granules and the control of mRNA translation

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