CUG-BP binds to RNA substrates and recruits PARN deadenylase.
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.
Moraes
Karen C M
KC
Department of Microbiology, Immunology & Pathology, College of Veterinary Medicine & Biomedical Sciences, Colorado State University, Fort Collins, 80523, USA.
Wilusz
Carol J
CJ
Wilusz
Jeffrey
J
D001483:Base Sequence; D000067879:CELF1 Protein; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000067879:CELF1 Protein; D005095:Exoribonucleases; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C102843:CELF1 protein, human