Genes misregulated in <i>C. elegans</i> deficient in Dicer, RDE-4, or RDE-1 are enriched for innate immunity genes

Welker, Noah C.; Habig, Jeffrey W.; Bass, Brenda

doi:10.1261/rna.542107

Cited by 53 publications

(62 citation statements)

References 56 publications

(76 reference statements)

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“…A recent microarray study reported gene expression changes in the RNAi pathway mutants rde-1, rde-4, and dcr-1 (20). We mapped the misregulated gene sets from this study to the functional groups of coregulated genes ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1). One difference between the studies is that we used L1-L2 larva and the published report used adult worms (20). Because adult worms contain both differentiated somatic tissues and actively proliferating and specialized germline cells, whereas the L1-L2 larvae contain primarily somatic cells, the resulting ''average'' gene expression profile is likely to be different in adults and larvae.…”

Section: Resultsmentioning

confidence: 99%

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RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans

Grishok

Hoersch

Sharp

2008

Proc. Natl. Acad. Sci. U.S.A.

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In Caenorhabditis elegans , a vast number of endogenous short RNAs corresponding to thousands of genes have been discovered recently. This finding suggests that these short interfering RNAs (siRNAs) may contribute to regulation of many developmental and other signaling pathways in addition to silencing viruses and transposons. Here, we present a microarray analysis of gene expression in RNA interference (RNAi)-related mutants rde-4 , zfp-1 , and alg-1 and the retinoblastoma (Rb) mutant lin-35 . We found that a component of Dicer complex RDE-4 and a chromatin-related zinc finger protein ZFP-1, not implicated in endogenous RNAi, regulate overlapping sets of genes. Notably, genes a) up-regulated in the rde-4 and zfp-1 mutants and b) up-regulated in the lin-35 (Rb) mutant, but not the down-regulated genes are highly represented in the set of genes with corresponding endogenous siRNAs (endo-siRNAs). Our study suggests that endogenous siRNAs cooperate with chromatin factors, either C. elegans ortholog of acute lymphoblastic leukemia-1 (ALL-1)-fused gene from chromosome 10 (AF10), ZFP-1, or tumor suppressor Rb, to regulate overlapping sets of genes and predicts a large role for RNAi-based chromatin silencing in control of gene expression in C. elegans .

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans

Grishok

Hoersch

Sharp

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…We found no evidence for an up-regulation of transposon RNA levels in a blanks mutant. However, similar to C. elegans RNAidefective mutants (36), blanks mutant testes exhibit an up-regulation of genes involved in innate immunity. Derepression of the retroelement lifecycle is often associated with sterility.…”

Section: Discussionmentioning

confidence: 94%

Blanks, a nuclear siRNA/dsRNA-binding complex component, is required for Drosophila spermiogenesis

Gerbasi

Preall

Golden

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Small RNAs and a diverse array of protein partners control gene expression in eukaryotes through a variety of mechanisms. By combining siRNA affinity chromatography and mass spectrometry, we have identified the double-stranded RNA-binding domain protein Blanks to be an siRNA-and dsRNA-binding protein from Drosophila S2 cells. We find that Blanks is a nuclear factor that contributes to the efficiency of RNAi. Biochemical fractionation of a Blanks-containing complex shows that the Blanks complex is unlike previously described RNA-induced silencing complexes and associates with the DEAD-box helicase RM62, a protein previously implicated in RNA silencing. In flies, Blanks is highly expressed in testes tissues and is necessary for postmeiotic spermiogenesis, but loss of Blanks is not accompanied by detectable transposon derepression. Instead, genes related to innate immunity pathways are up-regulated in blanks mutant testes. These results reveal Blanks to be a unique component of a nuclear siRNA/dsRNA-binding complex that contributes to essential RNA silencing-related pathways in the male germ line.

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“…Mutations in rde-4 have been associated with decreased life span (Welker et al 2007;Mansisidor et al 2011) and increased sensitivity to oxidative stress (Mansisidor et al 2011) and temperature (Blanchard et al 2011). An increase in stress sensitivity and reduced life span of rde-4 mutants has been attributed to the upregulation of pdk-1 (Mansisidor et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

Kennedy

Grishok

2014

Genetics

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Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphroditespecific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning.

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Genes misregulated in C. elegans deficient in Dicer, RDE-4, or RDE-1 are enriched for innate immunity genes

Cited by 53 publications

References 56 publications

RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans

RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans

Blanks, a nuclear siRNA/dsRNA-binding complex component, is required for Drosophila spermiogenesis

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

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