title: Interaction between a poly(A)-specific ribonuclease and the 5' cap influences mRNA deadenylation rates in vitro.
abstract: We have used an in vitro system that reproduces in vivo aspects of mRNA turnover to elucidate mechanisms of deadenylation. DAN, the major enzyme responsible for poly(A) tail shortening in vitro, specifically interacts with the 5' cap structure of RNA substrates, and this interaction is greatly stimulated by a poly(A) tail. Several observations suggest that cap-DAN interactions are functionally important for the networking between regulated mRNA stability and translation. First, uncapped RNA substrates are inefficiently deadenylated. Second, a stem-loop structure in the 5' UTR dramatically reduces deadenylation by interfering with cap-DAN interactions. Third, the addition of cap binding protein eIF4E inhibits deadenylation in vitro. These data provide insights into the early steps of substrate recognition that target an mRNA for degradation.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gao
authors.forename: D T
authors.initials: DT
authors.lastname: Fritz
authors.forename: L P
authors.initials: LP
authors.lastname: Ford
authors.forename: J
authors.initials: J
authors.lastname: Wilusz
mesh_terms: D039561:Eukaryotic Initiation Factor-4E; D005095:Exoribonucleases / Q000187:drug effects / Q000378:metabolism*; D008962:Models, Theoretical; D010448:Peptide Initiation Factors / Q000378:metabolism; D011061:Poly A / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D012314:RNA Cap Analogs / Q000494:pharmacology; D012315:RNA Caps / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D005095:Exoribonucleases; D010448:Peptide Initiation Factors; D011061:Poly A; D011506:Proteins; D012314:RNA Cap Analogs; D012315:RNA Caps; D012333:RNA, Messenger