期刊
MOLECULAR CELL
卷 44, 期 1, 页码 120-133出版社
CELL PRESS
DOI: 10.1016/j.molcel.2011.09.007
关键词
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资金
- Max Planck Society
- Deutsche Forschungsgemeinschaft (DFG) [FOR855]
- Gottfried Wilhelm Leibniz
- European Commission [LSHG-CT-2006-037900]
miRNAs are posttranscriptional regulators of gene expression that associate with Argonaute and GW182 proteins to repress translation and/or promote mRNA degradation. miRNA-mediated mRNA degradation is initiated by deadenylation, although it is not known whether deadenylases are recruited to the mRNA target directly or by default, as a consequence of a translational block. To answer this question, we performed a screen for potential interactions between the Argonaute and GW182 proteins and subunits of the two cytoplasmic deadenylase complexes. We found that human GW182 proteins recruit the PAN2-PAN3 and CCR4-CAF1-NOT deadenylase complexes through direct interactions with PAN3 and NOT1, respectively. These interactions are critical for silencing and are conserved in D. melanogaster. Our findings reveal that GW182 proteins provide a docking platform through which deadenylase complexes gain access to the poly(A) tail of miRNA targets to promote their deadenylation, and they further indicate that deadenylation is a direct effect of miRNA regulation.
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