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PMID:14961122

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Citation

Kennedy, S, Wang, D and Ruvkun, G (2004) A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature 427:645-9

Abstract

In many organisms, introducing double-stranded RNA (dsRNA) causes the degradation of messenger RNA that is homologous to the trigger dsRNA--a process known as RNA interference. The dsRNA is cleaved into short interfering RNAs (siRNAs), which hybridize to homologous mRNAs and induce their degradation. dsRNAs vary in their ability to trigger RNA interference: many mRNA-targeting dsRNAs show weak phenotypes, and nearly all mRNAs of the Caenorhabditis elegans nervous system are refractory to RNA interference. C. elegans eri-1 was identified in a genetic screen for mutants with enhanced sensitivity to dsRNAs. Here we show that eri-1 encodes an evolutionarily conserved protein with domains homologous to nucleic-acid-binding and exonuclease proteins. After exposure to dsRNA or siRNAs, animals with eri-1 mutations accumulate more siRNAs than do wild-type animals. C. elegans ERI-1 and its human orthologue degrade siRNAs in vitro. In the nematode worm, ERI-1 is predominantly cytoplasmic and is expressed most highly in the gonad and a subset of neurons, suggesting that ERI-1 siRNase activity suppresses RNA interference more intensely in these tissues. Thus, ERI-1 is a negative regulator that may normally function to limit the duration, cell-type specificity or endogenous functions of RNA interference.

Links

PubMed Online version:10.1038/nature02302

Keywords

Amino Acid Sequence; Animals; Caenorhabditis elegans/enzymology; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cloning, Molecular; Conserved Sequence; Cytoplasm/enzymology; Cytoplasm/metabolism; Exoribonucleases/chemistry; Exoribonucleases/genetics; Exoribonucleases/metabolism; Gonads/metabolism; Humans; Molecular Sequence Data; Mutation; Neurons/metabolism; Organ Specificity; RNA Interference; RNA, Double-Stranded/genetics; RNA, Double-Stranded/metabolism; RNA, Small Interfering/genetics; RNA, Small Interfering/metabolism; Ribonucleases/chemistry; Ribonucleases/genetics; Ribonucleases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:ERI1

involved_in

GO:0016246: RNA interference

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00088949
WB:WBVar00088956

P

Seeded From UniProt

complete

CAEEL:ERI1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:ERI1

involved_in

GO:0006401: RNA catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ERI1

enables

GO:0000175: 3'-5'-exoribonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:ERI1

enables

GO:0003676: nucleic acid binding

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q00839

F

Seeded From UniProt

complete

CAEEL:ERI1

involved_in

GO:0048609: multicellular organismal reproductive process

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00088949
WB:WBVar00088956

P

Seeded From UniProt

complete

CAEEL:ERI1

involved_in

GO:0045132: meiotic chromosome segregation

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00088949
WB:WBVar00088956

P

Seeded From UniProt

complete


See also

References

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