Pat1 Contains Distinct Functional Domains That Promote P-body Assembly and Activation of Decapping

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2007 Dec 19

PMID 18086885

Citations 67

Authors

Guy R Pilkington

Roy Parker

Affiliations

Soon will be listed here.

Abstract

The control of mRNA degradation and translation are important aspects of gene regulation. Recent results suggest that translation repression and mRNA decapping can be intertwined and involve the formation of a quiescent mRNP, which can accumulate in cytoplasmic foci referred to as P bodies. The Pat1 protein is a key component of this complex and an important activator of decapping, yet little is known about its function. In this work, we analyze Pat1 in Saccharomyces cerevisiae function by deletion and functional analyses. Our results identify two primary functional domains in Pat1: one promoting translation repression and P-body assembly and a second domain promoting mRNA decapping after assembly of the mRNA into a P-body mRNP. In addition, we provide evidence that Pat1 binds RNA and has numerous domain-specific interactions with mRNA decapping factors. These results indicate that Pat1 is an RNA binding protein and a multidomain protein that functions at multiple stages in the process of translation repression and mRNA decapping.

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References

Muhlrad D, Decker C, Parker R . Deadenylation of the unstable mRNA encoded by the yeast MFA2 gene leads to decapping followed by 5'-->3' digestion of the transcript. Genes Dev. 1994; 8(7):855-66. DOI: 10.1101/gad.8.7.855. View

Tharun S, Parker R . Targeting an mRNA for decapping: displacement of translation factors and association of the Lsm1p-7p complex on deadenylated yeast mRNAs. Mol Cell. 2001; 8(5):1075-83. DOI: 10.1016/s1097-2765(01)00395-1. View

Parker R, Song H . The enzymes and control of eukaryotic mRNA turnover. Nat Struct Mol Biol. 2004; 11(2):121-7. DOI: 10.1038/nsmb724. View

Beliakova-Bethell N, Beckham C, Giddings Jr T, Winey M, Parker R, Sandmeyer S . Virus-like particles of the Ty3 retrotransposon assemble in association with P-body components. RNA. 2005; 12(1):94-101. PMC: 1370889. DOI: 10.1261/rna.2264806. View

Coller J, Parker R . Eukaryotic mRNA decapping. Annu Rev Biochem. 2004; 73:861-90. DOI: 10.1146/annurev.biochem.73.011303.074032. View

Schwartz D, Parker R . Mutations in translation initiation factors lead to increased rates of deadenylation and decapping of mRNAs in Saccharomyces cerevisiae. Mol Cell Biol. 1999; 19(8):5247-56. PMC: 84368. DOI: 10.1128/MCB.19.8.5247. View

LaGrandeur T, Parker R . The cis acting sequences responsible for the differential decay of the unstable MFA2 and stable PGK1 transcripts in yeast include the context of the translational start codon. RNA. 1999; 5(3):420-33. PMC: 1369770. DOI: 10.1017/s1355838299981748. View

Teixeira D, Sheth U, Valencia-Sanchez M, Brengues M, Parker R . Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA. 2005; 11(4):371-82. PMC: 1370727. DOI: 10.1261/rna.7258505. View

Eulalio A, Behm-Ansmant I, Izaurralde E . P bodies: at the crossroads of post-transcriptional pathways. Nat Rev Mol Cell Biol. 2006; 8(1):9-22. DOI: 10.1038/nrm2080. View

10.

Beelman C, Stevens A, Caponigro G, LaGrandeur T, Hatfield L, Fortner D . An essential component of the decapping enzyme required for normal rates of mRNA turnover. Nature. 1996; 382(6592):642-6. DOI: 10.1038/382642a0. View

11.

Meyer S, Temme C, Wahle E . Messenger RNA turnover in eukaryotes: pathways and enzymes. Crit Rev Biochem Mol Biol. 2004; 39(4):197-216. DOI: 10.1080/10409230490513991. View

12.

Coller J, Parker R . General translational repression by activators of mRNA decapping. Cell. 2005; 122(6):875-86. PMC: 1853273. DOI: 10.1016/j.cell.2005.07.012. View

13.

Muhlrad D, Parker R . Recognition of yeast mRNAs as "nonsense containing" leads to both inhibition of mRNA translation and mRNA degradation: implications for the control of mRNA decapping. Mol Biol Cell. 1999; 10(11):3971-8. PMC: 25692. DOI: 10.1091/mbc.10.11.3971. View

14.

Wyers F, Minet M, Dufour M, Vo L, Lacroute F . Deletion of the PAT1 gene affects translation initiation and suppresses a PAB1 gene deletion in yeast. Mol Cell Biol. 2000; 20(10):3538-49. PMC: 85646. DOI: 10.1128/MCB.20.10.3538-3549.2000. View

15.

Liu J, Valencia-Sanchez M, Hannon G, Parker R . MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol. 2005; 7(7):719-23. PMC: 1855297. DOI: 10.1038/ncb1274. View

16.

Lykke-Andersen J . Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay. Mol Cell Biol. 2002; 22(23):8114-21. PMC: 134073. DOI: 10.1128/MCB.22.23.8114-8121.2002. View

17.

Holmes L, Campbell S, De Long S, Sachs A, Ashe M . Loss of translational control in yeast compromised for the major mRNA decay pathway. Mol Cell Biol. 2004; 24(7):2998-3010. PMC: 371117. DOI: 10.1128/MCB.24.7.2998-3010.2004. View

18.

Cougot N, Babajko S, Seraphin B . Cytoplasmic foci are sites of mRNA decay in human cells. J Cell Biol. 2004; 165(1):31-40. PMC: 2172085. DOI: 10.1083/jcb.200309008. View

19.

Jakymiw A, Lian S, Eystathioy T, Li S, Satoh M, Hamel J . Disruption of GW bodies impairs mammalian RNA interference. Nat Cell Biol. 2005; 7(12):1267-74. DOI: 10.1038/ncb1334. View

20.

Caponigro G, Parker R . Multiple functions for the poly(A)-binding protein in mRNA decapping and deadenylation in yeast. Genes Dev. 1995; 9(19):2421-32. DOI: 10.1101/gad.9.19.2421. View