DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs

Fukuda, Tsuyoshi; Yamagata, Kazuya; Fujiyama, Sally; Μatsumoto, Takahiro; Koshida, Iori; Yoshimura, Kimihiro; Mihara, Makoto; Naitou, Masanori; Endoh, Hideki; Nakamura, Takashi; Akimoto, Chihiro; Yamamoto, Yasutake; Katagiri, Takenobu; Foulds, Charles E.; Takezawa, Shinichiro; Kitagawa, Hirochika; Takeyama, Ken Ichi; O’Malley, Bert W.; Kato, Shigeaki

doi:10.1038/ncb1577

Cited by 398 publications

(345 citation statements)

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“…Mice lacking the ATP-dependent DEAD-box RNA helicases Ddx5 or Ddx17 also show defects in 5.8S rRNA production and early lethality 19 . Ddx5 −/− mice do not survive past E11.5, Ddx17 −/− mice die within 2 d following birth with reduced body size and Ddx17 −/− MEF cells show reduced proliferation in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Ddx5 −/− mice do not survive past E11.5, Ddx17 −/− mice die within 2 d following birth with reduced body size and Ddx17 −/− MEF cells show reduced proliferation in vitro. Like Eri1, Ddx5 and Ddx17 perform important functions in 5.8S rRNA biogenesis and short regulatory RNA homeostasis 19 . Both helicases are found in a complex with the RNase III enzyme Drosha, which is responsible for cropping the hairpins of pre-miRNAs from primary miRNA transcripts 30,31 .…”

Section: Discussionmentioning

confidence: 99%

“…Drosha localizes to the nucleus and also transits into the nucleolus during S phase 32 . Mouse embryos deficient for either Ddx5 or Ddx17 have reduced levels of 5.8S rRNA and most miRNAs, and this phenotype can be reproduced using siRNAs that target Ddx5, Ddx17 or Drosha in MEFs and HeLa cells 19,33 . Considering the dual involvement of Eri1, Drosha, Ddx5 and Ddx17 in rRNA processing and the RNAi pathway, one may speculate that, during evolution, factors that were primarily involved in rRNA processing later acquired new functions in the biogenesis and regulation of short regulatory RNA molecules.…”

Section: Discussionmentioning

confidence: 99%

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Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing

Ansel

Pastor

Rath

et al. 2008

Nat Struct Mol Biol

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Eri1 is a 3′-to-5′ exoribonuclease conserved from fission yeast to humans. Here we show that Eri1 associates with ribosomes and ribosomal RNA (rRNA). Ribosomes from Eri1-deficient mice contain 5.8S rRNA that is aberrantly extended at its 3′ end, and Eri1, but not a catalytically inactive mutant, converts this abnormal 5.8S rRNA to the wild-type form in vitro and in cells. In human and murine cells, Eri1 localizes to the cytoplasm and nucleus, with enrichment in the nucleolus, the site of preribosome biogenesis. RNA binding residues in the Eri1 SAP and linker domains promote stable association with rRNA and thereby facilitate 5.8S rRNA 3′ end processing. Taken together, our findings indicate that Eri1 catalyzes the final trimming step in 5.8S rRNA processing, functionally and spatially connecting this regulator of RNAi with the basal translation machinery.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing

Ansel

Pastor

Rath

et al. 2008

Nat Struct Mol Biol

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“…Previously, the microRNA processor Drosha and two DEAD-box helicases were shown to act in both rRNA biogenesis and small-RNA-dependent silencing 13 . Our data exposes more extensive integration between these two cellular pathways, and suggests that future analyses may uncover additional common components and origins of these pathways.…”

Section: Online)mentioning

confidence: 99%

The exonuclease ERI-1 has a conserved dual role in 5.8S rRNA processing and RNAi

Gabel

Ruvkun

2008

Nat Struct Mol Biol

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The exonuclease ERI-1 negatively regulates RNA interference (RNAi) in Caenorhabiditis elegans and Schizosaccharomyces pombe, and is required for production of some C. elegans endogenous small-interfering RNAs. We show that ERI-1 performs 3′ end processing of the 5.8S ribosomal RNA (rRNA) in both C. elegans and S. pombe. In C. elegans, two protein isoforms of ERI-1 are localized to the cytoplasm, and each has distinct functions in rRNA processing and negative regulation of RNAi.The C. elegans eri-1 gene encodes a 3′ to 5′ exonuclease of the DEDDh superfamily of RNase T exonucleases that was identified as a negative regulator of RNA interference (RNAi) 1 . Mutations in eri-1 cause an enhanced RNA interference (Eri) phenotype by which double stranded RNAs (dsRNAs) that are ineffective in silencing target mRNAs in wildtype animals trigger robust silencing in the Eri mutant. In the fission yeast S. pombe loss of Eri1 causes increased levels of small interfering RNAs (siRNAs) corresponding to centromeric repeats and a concomitant increase in RNAi-dependent heterochromatin formation at these genomic loci 2 . Analysis of ERI-1 in C. elegans, human and fission yeast has shown that it can degrade the 3′ end of siRNAs and histone mRNAs in vitro [1][2][3][4] , but in vivo substrates for this conserved enzyme are poorly understood.In the course of the analysis of RNAs isolated from the eri-1 null mutant, we observed that the 5.8S rRNA in an eri-1 worm is longer than wild-type 5.8S rRNA (Fig. 1a). This length difference is present in all detectable 5.8S rRNA, suggesting that eri-1 mutants have an rRNA processing defect in most, if not all, cells. The mature 5.8S, 18S, and 25-28S rRNAs in eukaryotes are generated from a 35S-47S precursor RNA via a series of processing steps mediated by multiple nucleases 5 . The activity of ERI-1 as a 3′ to 5′ exonuclease [1][2][3][4] suggests that the longer 5.8S rRNA is due to an extension of the 3′ end. RNase H cleavage and 3′ end cloning on the 5.8S rRNA of wild-type and mutant C. elegans indicated that all eri-1 5.8S rRNA is at least 1 nucleotide longer than the wild-type 5.8S rRNA specifically at the 3′ end, with a substantial fraction of eri-1 5.8S rRNA containing 2 to 4 additional nucleotides ( Supplementary Fig. 1 online). The 5.8S processing defect was observed in two independently derived eri-1 alleles, including another null allele (mg388, data not shown), and is rescued by an eri-1 transgene (see below), proving that loss of eri-1 causes the 5.8S processing defect. The 5.8S processing defect was not observed in other enhanced RNAi mutants with pleiotropies in common with eri-11 ,6 (data not shown). To characterize whether ERI-1 function in rRNA trimming is an ancient feature of this orthology group, we examined the 5.8S rRNA in the S. pombe erilΔ mutant and observed a length defect similar to the C. elegans eri-1 mutant (Fig. 1b). RNase H and sequencing analysis revealed a 3′ extended 5.8S rRNA species in erilΔ containing from 2 to 8 additional 3′ nucleotides ( Supplement...

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“…The primary transcripts of miRNA (pri-miRNA) are cleaved into precursor miRNA (pre-miRNA) by nuclear DROSHA (RNASEN) ribonuclease type III (RNase III), and further processed to mature miRNAs by cytoplasmic DICER1 RNase III in mammalian miRNA biogenesis. The DROSHA complex consists of DROSHA, DGCR8 (DiGeorge syndrome critical region gene 8), DDX5 (RNA helicase p68), and DDX17 (RNA helicase p72; Lee et al, 2003;Fukuda et al, 2007). Recently, additional molecules were shown to be involved in miRNA maturation; e.g., the TGF- signal transducer Smads promotes miR-21 maturation, and the tumor suppressor p53 enhances the processing of miR-16, miR-143, miR-145, and miR-206 (Davis et al, 2008;Suzuki et al, 2009), whereas estrogen receptor  attenuates maturation of pri-miRNAs into pre-miRNAs .…”

Section: Introductionmentioning

confidence: 99%