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

Marc R. Fabian; Maja K. Cieplak; Filipp Frank; Masahiro Morita; Jonathan Green; Tharan Srikumar; Bhushan Nagar; Tadashi Yamamoto; Brian Raught; Thomas F. Duchaine; Nahum Sonenberg

doi:10.1038/nsmb.2149

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

Marc R. Fabian, Maja K. Cieplak, Filipp Frank, Masahiro Morita, Jonathan Green, Tharan Srikumar, Bhushan Nagar, Tadashi Yamamoto, Brian Raught, Thomas F. Duchaine, Nahum Sonenberg

Research output: Contribution to journal › Article › peer-review

258 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1211-1217
Number of pages	7
Journal	Nature Structural and Molecular Biology
Volume	18
Issue number	11
DOIs	https://doi.org/10.1038/nsmb.2149
State	Published - Nov 2011
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Structural Biology

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title = "MiRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT",

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.",

author = "Fabian, {Marc R.} and Cieplak, {Maja K.} and Filipp Frank and Masahiro Morita and Jonathan Green and Tharan Srikumar and Bhushan Nagar and Tadashi Yamamoto and Brian Raught and Duchaine, {Thomas F.} and Nahum Sonenberg",

year = "2011",

month = nov,

doi = "10.1038/nsmb.2149",

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T1 - MiRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT

AU - Fabian, Marc R.

AU - Cieplak, Maja K.

AU - Frank, Filipp

AU - Morita, Masahiro

AU - Green, Jonathan

AU - Srikumar, Tharan

AU - Nagar, Bhushan

AU - Yamamoto, Tadashi

AU - Raught, Brian

AU - Duchaine, Thomas F.

AU - Sonenberg, Nahum

PY - 2011/11

Y1 - 2011/11

N2 - 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.

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

Abstract

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