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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.

SUBMITTER: Brook M

PROVIDER: S-EPMC3298439 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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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.

Brook Matthew M McCracken Lora L Reddington James P JP Lu Zhi-Liang ZL Morrice Nicholas A NA Gray Nicola K NK

The Biochemical journal 20120201 3

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, iden ...[more]

PMID: 22004688

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Project description:There is a great deal of interest in personalized, individualized, or precision interventions for disease and health-risk mitigation. This is as true of nutrition-based intervention and prevention strategies as it is for pharmacotherapies and pharmaceutical-oriented prevention strategies. Essentially, technological breakthroughs have enabled researchers to probe an individual's unique genetic, biochemical, physiological, behavioral, and exposure profile, allowing them to identify very specific and often nuanced factors that an individual might possess, which may make it more or less likely that he or she responds favorably to a particular intervention (e.g., nutrient supplementation) or disease prevention strategy (e.g., specific diet). However, as compelling and intuitive as personalized nutrition might be in the current era in which data-intensive biomedical characterization of individuals is possible, appropriately and objectively vetting personalized nutrition strategies is not trivial and requires novel study designs and data analytical methods. These designs and methods must consider a very integrated use of the multiple contemporary biomedical assays and technologies that motivate them, which adds to their complexity. Single-subject or N-of-1 trials can be used to assess the utility of personalized interventions and, in addition, can be crafted in such a way as to accommodate the necessarily integrated use of many emerging biomedical technologies and assays. In this review, we consider the motivation, design, and implementation of N-of-1 trials in translational nutrition research that are meant to assess the utility of personalized nutritional strategies. We provide a number of example studies, discuss appropriate analytical methods given the complex data they generate and require, and consider how such studies could leverage integration of various biomarker assays and clinical end points. Importantly, we also consider the development of strategies and algorithms for matching nutritional needs to individual biomedical profiles and the issues surrounding them. Finally, we discuss the limitations of personalized nutrition studies, possible extensions of N-of-1 nutritional intervention studies, and areas of future research.

Dataset Information

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.

Publications

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.

Similar Datasets

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