Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies

@article{Sen2005Argonaute2R,
  title={Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies},
  author={George L. Sen and Helen M. Blau},
  journal={Nature Cell Biology},
  year={2005},
  volume={7},
  pages={633-636}
}
  • G. Sen, H. Blau
  • Published 22 May 2005
  • Biology, Medicine
  • Nature Cell Biology
RNA interference (RNAi) is an important means of eliminating mRNAs, but the intracellular location of RNA-induced silencing complex (RISC) remains unknown. We show here that Argonaute 2, a key component of RISC, is not randomly distributed but concentrates in mRNA decay centres that are known as cytoplasmic bodies. The localization of Argonaute 2 in decay centres is not altered by the presence or absence of small interfering RNAs or their targeted mRNAs. However, RNA is required for the… Expand
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References

SHOWING 1-10 OF 19 REFERENCES
Argonaute2 Is the Catalytic Engine of Mammalian RNAi
TLDR
The evidence supports a model in which Argonaute contributes “Slicer” activity to RISC, providing the catalytic engine for RNAi. Expand
Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome.
TLDR
The findings indicate that mRNAs targeted by siRNAs are degraded from the ends generated by RISC cleavage, without undergoing decapping or deadenylation. Expand
A Link Between mRNA Turnover and RNA Interference in Arabidopsis
TLDR
It is proposed that mRNAs lacking a cap structure become exposed to RdRp to initiate or maintain RNAi, and it is shown that RdRP-dependent transgene silencing in Arabidopsis was caused by mutation of XRN4. Expand
Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs.
TLDR
The authors' results suggest that miRNAs are incorporated indiscriminately of their sequence into Ago1 through Ago4 containing microRNPs (miRNPs), and the specific role of Ago2 in guiding target RNA cleavage was confirmed by siRNA-based depletion of individual Ago members in combination with a sensitive positive-readout reporter assay. Expand
Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability
AU-rich elements (AREs) in the 3' untranslated region (UTR) of unstable mRNAs dictate their degradation. An RNAi-based screen performed in Drosophila S2 cells has revealed that Dicer1, Argonaute1Expand
Processing bodies require RNA for assembly and contain nontranslating mRNAs.
TLDR
In vivo and in vitro analysis indicates that P-bodies are dynamic structures that contain nontranslating mRNAs and function during cellular responses to stress, and results suggest additional biological roles of P- bodies in addition to being sites of mRNA degradation. Expand
Decapping and Decay of Messenger RNA Occur in Cytoplasmic Processing Bodies
TLDR
The flux of mRNAs between polysomes and P bodies is defined as a critical aspect of cytoplasmic mRNA metabolism and a possible site for regulation of mRNA degradation. Expand
Uncoupling of RNAi from active translation in mammalian cells.
TLDR
The results demonstrate that neither active translation nor unidirectional scanning is required for siRNA mediated target degradation, and nontranslated mRNAs are highly susceptible to RNAi, and blocking scanning from both the 5' and 3' ends of an mRNA does not impede RNAi. Expand
Cytoplasmic foci are sites of mRNA decay in human cells
TLDR
The occurrence of 5′–3′ mRNA decay in specific subcellular locations in human cells suggests that the cytoplasm of eukaryotic cells may be more organized than previously anticipated. Expand
A Dicer-2-Dependent 80S Complex Cleaves Targeted mRNAs during RNAi in Drosophila
TLDR
The results establish an ordered biochemical pathway for RISC assembly and indicate that siRNAs must first interact with Dcr-2 to reach the R3 "holo-RISC" complex, indicating that its role extends beyond the initiation phase of RNAi. Expand
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