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miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT

Fabian, Marc R, Cieplak, Maja K, Frank, Filipp, Morita, Masahiro, Green, Jonathan, Srikumar, Tharan, Nagar, Bhushan, Yamamoto, Tadashi, Raught, Brian, Duchaine, Thomas F, Sonenberg, Nahum·2011·Nature Structural & Molecular Biology
DOI 10.1038/nsmb.2149
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Abstract

miRNAs recruit the miRNA-induced silencing complex (miRISC), which includes Argonaute and GW182 as core proteins. GW182 proteins effect translational repression and deadenylation of target mRNAs. However, the molecular mechanisms of GW182-mediated repression remain obscure. We show here that human GW182 independently interacts with the PAN2-PAN3 and CCR4-NOT deadenylase complexes. Interaction of GW182 with CCR4-NOT is mediated by two newly discovered phylogenetically conserved motifs. Although either motif is sufficient to bind CCR4-NOT, only one of them can promote processive deadenylation of target mRNAs. Thus, GW182 serves as both a platform that recruits deadenylases and as a deadenylase coactivator that facilitates the removal of the poly(A) tail by CCR4-NOT.

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  • AUF1 mediates deadenylation of SNCA mRNA by directly recruiting the CNOT1-CNOT7 complex to the SNCA 3′UTR and not through the miR7/153-GW182-CNOT1 pathway.

    “These findings indicate that AUF1 mediates the deadenylation of SNCA mRNA by directly recruiting the CNOT1-CNOT7 complex to SNCA 3′UTR and not through the miR7/153-GW182-CNOT1 pathway [23].”

    From RNA binding protein AUF1/HNRNPD regulates nuclear export, stability and translation of SNCA transcripts (2023) · cites this paper as [23]

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Research works printed but not linked: 40

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Metadata

Authors
Fabian, M. R., Cieplak, M. K., Frank, F., Morita, M., Green, J., Srikumar, T., Nagar, B., Yamamoto, T., Raught, B., Duchaine, T. F., & Sonenberg, N.
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2011-10-07
Volume
18
Issue
11
Pages
1211-1217
ISSN
  • 1545-9993
  • 1545-9985
DOI
10.1038/nsmb.2149
Cited by
329
References
3
Language
en
Update notices
erratum (2012-03-05)
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