Projects per year
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.
|Number of pages||10|
|Publication status||Published - Feb 2012|
- mRNA translation
- poly(A)-binding protein (PABP)
- poly(A)-binding-protein-interacting motif 2 (PAM2)–poly(A)binding protein C-terminal domain (PABC) interaction
- posttranscriptional control, post-translational modification
- RNA-binding protein
FingerprintDive into the research topics of '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'. Together they form a unique fingerprint.
- 1 Finished
Poly (A)-binding proteins highlighted the importance of regulated mRNA translation and stability in determing a functional materno-fetal interface
Gray, N., Girardi, G. & Norman, J.
1/04/12 → 30/09/17