title: The multifunctional poly(A)-binding protein (PABP) 1 is subject to extensive dynamic post-translational modification, which molecular modelling suggests plays an important role in co-ordinating its activities.
abstract: PABP1 [poly(A)-binding protein 1] is a central regulator of mRNA translation and stability and is required for miRNA (microRNA)-mediated regulation and nonsense-mediated decay. Numerous protein, as well as RNA, interactions underlie its multi-functional nature; however, it is unclear how its different activities are co-ordinated, since many partners interact via overlapping binding sites. In the present study, we show that human PABP1 is subject to elaborate post-translational modification, identifying 14 modifications located throughout the functional domains, all but one of which are conserved in mouse. Intriguingly, PABP1 contains glutamate and aspartate methylations, modifications of unknown function in eukaryotes, as well as lysine and arginine methylations, and lysine acetylations. The latter dramatically alter the pI of PABP1, an effect also observed during the cell cycle, suggesting that different biological processes/stimuli can regulate its modification status, although PABP1 also probably exists in differentially modified subpopulations within cells. Two lysine residues were differentially acetylated or methylated, revealing that PABP1 may be the first example of a cytoplasmic protein utilizing a 'methylation/acetylation switch'. Modelling using available structures implicates these modifications in regulating interactions with individual PAM2 (PABP-interacting motif 2)-containing proteins, suggesting a direct link between PABP1 modification status and the formation of distinct mRNP (messenger ribonucleoprotein) complexes that regulate mRNA fate in the cytoplasm.
authors: MRC Centre for Reproductive Health/MRC Human Reproductive Sciences Unit, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK. matt.brook@ed.ac.uk
authors: Matthew
authors: M
authors: Brook
authors: Lora
authors: L
authors: McCracken
authors: James P
authors: JP
authors: Reddington
authors: Zhi-Liang
authors: ZL
authors: Lu
authors: Nicholas A
authors: NA
authors: Morrice
authors: Nicola K
authors: NK
authors: Gray
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008745:Methylation; D051379:Mice; D008958:Models, Molecular; D039122:Poly(A)-Binding Protein I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011496:Protein Methyltransferases / Q000378:metabolism / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D039122:Poly(A)-Binding Protein I; D001120:Arginine; D011496:Protein Methyltransferases