title: Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability.
abstract: PARN, a poly(A)-specific ribonuclease, binds the 5' cap-structure of mRNA and initiates deadenylation-dependent decay. Eukaryotic initiation factor 4E (eIF4E) also binds to the cap structure, an interaction that is critical for initiating cap-dependent translation. The stability of various mRNA transcripts in human cell lines is reduced under conditions of serum starvation as determined by both functional and chemical half-lives. Serum starvation also leads to enhanced cap association by PARN. In contrast, the 5' cap occupancy by eIF4E decreases under serum-deprivation, as does the translation of reporter transcripts. Further, we show that PARN is a phosphoprotein and that this modification can be modulated by serum status. Taken together, these data are consistent with a natural competition existing at the 5' cap structure between PARN and eIF4E that may be regulated by changes in post-translational modifications. These phosphorylation-induced changes in the interplay of PARN and eIF4E may determine whether the mRNA is translated or decayed.
authors.affiliation: Department of Neurology, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Seal
authors.forename: Richard
authors.initials: R
authors.lastname: Temperley
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wilusz
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lightowlers
authors.forename: Zofia M A
authors.initials: ZM
authors.lastname: Chrzanowska-Lightowlers
mesh_terms: D002460:Cell Line; D016895:Culture Media, Serum-Free; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005095:Exoribonucleases / Q000378:metabolism*; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012315:RNA Caps / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D016895:Culture Media, Serum-Free; D039561:Eukaryotic Initiation Factor-4E; D005095:Exoribonucleases; D010750:Phosphoproteins; D012315:RNA Caps; D012333:RNA, Messenger