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PUF proteins bind Pop2p to regulate messenger RNAs

Abstract

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.

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Figure 1: Mpt5p repression is dependent on POP2.
Figure 2: Mpt5p regulates decay of HO mRNA in vivo.
Figure 3: Mpt5p directly binds Pop2p.
Figure 4: Mpt5p enhances deadenylation in vitro.
Figure 5: Conservation of PUF-Pop2p interaction.
Figure 6: Model of Mpt5p-mediated repression.

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Acknowledgements

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.).

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Correspondence to Marvin Wickens.

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Goldstrohm, A., Hook, B., Seay, D. et al. PUF proteins bind Pop2p to regulate messenger RNAs. Nat Struct Mol Biol 13, 533–539 (2006). https://doi.org/10.1038/nsmb1100

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