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Human Pat1b Connects Deadenylation with mRNA Decapping and Controls the Assembly of Processing Bodies.

Ozgur, Sevim, Chekulaeva, Marina and Stoecklin, Georg (2010) Human Pat1b Connects Deadenylation with mRNA Decapping and Controls the Assembly of Processing Bodies. Molecular and Cellular Biology, 30 (17). pp. 4308-4323. ISSN 1098-5549

Abstract

In eukaryotic cells, degradation of many mRNAs is initiated by removal of the poly(A) tail followed by decapping and 5'-3' exonucleolytic decay. Although the order of these events is well established, we are still lacking a mechanistic understanding of how deadenylation and decapping are linked. In this report we identify human Pat1b as a protein that is tightly associated with the Ccr4-Caf1-Not deadenylation complex as well as with the Dcp1-Dcp2 decapping complex. In addition, the RNA helicase Rck and Lsm1 proteins interact with human Pat1b. These interactions are mediated via at least three independent domains within Pat1b, suggesting that Pat1b serves as a scaffold protein. By tethering Pat1b to a reporter mRNA, we further provide evidence that Pat1b is also functionally linked to both deadenylation and decapping. Finally, we report that Pat1b strongly induces the formation of processing (P) bodies, cytoplasmic foci that contain most enzymes of the RNA decay machinery. An amino-terminal region within Pat1b serves as an aggregation-prone domain that nucleates P bodies, whereas an acidic domain controls the size of P bodies. Taken together, these findings provide evidence that human Pat1b is a central component of the RNA decay machinery by physically connecting deadenylation with decapping.

Item Type: Article
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Date Deposited: 04 Dec 2010 00:45
Last Modified: 04 Dec 2010 00:45
URI: https://oak.novartis.com/id/eprint/3960

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