PUF proteins, a family of RNA-binding proteins, interact with the 3′ untranslated regions (UTRs) of specific mRNAs to control their translation and stability. PUF protein action is commonly correlated with removal of the poly(A) tail of target mRNAs. Here, we focus on how PUF proteins enhance deadenylation and mRNA decay. We show that a yeast PUF protein physically binds Pop2p, which is a component of the Ccr4p-Pop2p-Not deadenylase complex, and that Pop2p is required for PUF repression activity. By binding Pop2p, the PUF protein simultaneously recruits the Ccr4p deadenylase and two other enzymes involved in mRNA regulation, Dcp1p and Dhh1p. We reconstitute regulated deadenylation in vitro and demonstrate that the PUF-Pop2p interaction is conserved in yeast, worms and humans. We suggest that the PUF-Pop2p interaction underlies regulated deadenylation, mRNA decay and repression by PUF proteins.
|Original language||English (US)|
|Number of pages||7|
|Journal||Nature Structural and Molecular Biology|
|State||Published - Jun 26 2006|
Bibliographical noteFunding Information:
We thank A. Ansari and J. Kimble for helpful comments on the manuscript and all members of the Wickens lab for discussions and suggestions. We also thank T. Tadauchi (Nagoya University) for plasmid YEp195 MPT5 and yeast strain TTC59. We appreciate the work of L. Vanderploeg in preparing figures. This work was supported by the US National Institutes of Health (postdoctoral fellowship to A.C.G. and research grant to M.W.).