CUG-BP Binds to RNA Substrates and Recruits PARN Deadenylase

Overview

Journal RNA

Specialty Molecular Biology

Date 2006 Apr 8

PMID 16601207

Citations 99

Authors

Karen C M Moraes

Carol J Wilusz

Jeffrey Wilusz

Affiliations

Soon will be listed here.

Abstract

CUG-BP is the human homolog of the Xenopus EDEN-BP, which was shown previously to bind to mRNAs, such as c-mos, that exhibit rapid deadenylation following fertilization of the oocyte. While several studies have focused on roles of CUG-BP as a splicing or translation regulator in mammalian cells, its role in mRNA decay has not been examined in detail. Here, we have used an in vitro deadenylation assay to dissect the function of CUG-BP in the decay of two ARE-containing mRNAs: c-fos and TNFalpha. CUG-BP binds specifically to both of these RNAs and stimulates poly(A) shortening by PARN. Moreover, CUG-BP interacts with PARN in extracts by coimmunoprecipitation, and this interaction can be recapitulated using recombinant proteins. CUG-BP, therefore, is the first RNA-binding protein shown to directly recruit a deadenylase to an RNA substrate.

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References

Lu X, Timchenko N, Timchenko L . Cardiac elav-type RNA-binding protein (ETR-3) binds to RNA CUG repeats expanded in myotonic dystrophy. Hum Mol Genet. 1999; 8(1):53-60. DOI: 10.1093/hmg/8.1.53. View

Paillard L, Legagneux V, Osborne H . A functional deadenylation assay identifies human CUG-BP as a deadenylation factor. Biol Cell. 2003; 95(2):107-13. DOI: 10.1016/s0248-4900(03)00010-8. View

Legagneux V, Omilli F, Osborne H . Substrate-specific regulation of RNA deadenylation in Xenopus embryo and activated egg extracts. RNA. 1995; 1(10):1001-8. PMC: 1369326. View

Faustino N, Cooper T . Identification of putative new splicing targets for ETR-3 using sequences identified by systematic evolution of ligands by exponential enrichment. Mol Cell Biol. 2005; 25(3):879-87. PMC: 544011. DOI: 10.1128/MCB.25.3.879-887.2005. View

Gherzi R, Lee K, Briata P, Wegmuller D, Moroni C, Karin M . A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Mol Cell. 2004; 14(5):571-83. DOI: 10.1016/j.molcel.2004.05.002. View

Lykke-Andersen J, Wagner E . Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1. Genes Dev. 2005; 19(3):351-61. PMC: 546513. DOI: 10.1101/gad.1282305. View

Wilusz J, Shenk T . A 64 kd nuclear protein binds to RNA segments that include the AAUAAA polyadenylation motif. Cell. 1988; 52(2):221-8. DOI: 10.1016/0092-8674(88)90510-7. View

Richter J . Cytoplasmic polyadenylation in development and beyond. Microbiol Mol Biol Rev. 1999; 63(2):446-56. PMC: 98972. DOI: 10.1128/MMBR.63.2.446-456.1999. View

Paillard L, Omilli F, Legagneux V, Bassez T, Maniey D, Osborne H . EDEN and EDEN-BP, a cis element and an associated factor that mediate sequence-specific mRNA deadenylation in Xenopus embryos. EMBO J. 1998; 17(1):278-87. PMC: 1170378. DOI: 10.1093/emboj/17.1.278. View

10.

Mukherjee D, Gao M, OConnor J, Raijmakers R, Pruijn G, Lutz C . The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements. EMBO J. 2002; 21(1-2):165-74. PMC: 125812. DOI: 10.1093/emboj/21.1.165. View

11.

Dignam J, Lebovitz R, Roeder R . Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983; 11(5):1475-89. PMC: 325809. DOI: 10.1093/nar/11.5.1475. View

12.

Voeltz G, Steitz J . AUUUA sequences direct mRNA deadenylation uncoupled from decay during Xenopus early development. Mol Cell Biol. 1998; 18(12):7537-45. PMC: 109334. DOI: 10.1128/MCB.18.12.7537. View

13.

Ford L, Wilusz J . An in vitro system using HeLa cytoplasmic extracts that reproduces regulated mRNA stability. Methods. 1999; 17(1):21-7. DOI: 10.1006/meth.1998.0703. View

14.

Detivaud L, Pascreau G, Karaiskou A, Osborne H, Kubiak J . Regulation of EDEN-dependent deadenylation of Aurora A/Eg2-derived mRNA via phosphorylation and dephosphorylation in Xenopus laevis egg extracts. J Cell Sci. 2003; 116(Pt 13):2697-705. DOI: 10.1242/jcs.00477. View

15.

Audic Y, Omilli F, Osborne H . Embryo deadenylation element-dependent deadenylation is enhanced by a cis element containing AUU repeats. Mol Cell Biol. 1998; 18(12):6879-84. PMC: 109271. DOI: 10.1128/MCB.18.12.6879. View

16.

Ford L, Watson J, Keene J, Wilusz J . ELAV proteins stabilize deadenylated intermediates in a novel in vitro mRNA deadenylation/degradation system. Genes Dev. 1999; 13(2):188-201. PMC: 316394. DOI: 10.1101/gad.13.2.188. View

17.

Timchenko N, Wang G, Timchenko L . RNA CUG-binding protein 1 increases translation of 20-kDa isoform of CCAAT/enhancer-binding protein beta by interacting with the alpha and beta subunits of eukaryotic initiation translation factor 2. J Biol Chem. 2005; 280(21):20549-57. DOI: 10.1074/jbc.M409563200. View

18.

Paillard L, Legagneux V, Maniey D, Osborne H . c-Jun ARE targets mRNA deadenylation by an EDEN-BP (embryo deadenylation element-binding protein)-dependent pathway. J Biol Chem. 2001; 277(5):3232-5. DOI: 10.1074/jbc.M109362200. View

19.

Roberts R, Timchenko N, Miller J, Reddy S, Caskey C, Swanson M . Altered phosphorylation and intracellular distribution of a (CUG)n triplet repeat RNA-binding protein in patients with myotonic dystrophy and in myotonin protein kinase knockout mice. Proc Natl Acad Sci U S A. 1997; 94(24):13221-6. PMC: 24290. DOI: 10.1073/pnas.94.24.13221. View

20.

Timchenko L, Miller J, Timchenko N, DeVore D, Datar K, Lin L . Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res. 1996; 24(22):4407-14. PMC: 146274. DOI: 10.1093/nar/24.22.4407. View