Nuclear relocalisation of cytoplasmic poly(A)-binding proteins PABP1 and PABP4 in response to UV irradiation reveals mRNA-dependent export of metazoan PABPs

Burgess, H. M., Richardson, W. A., Anderson, R. C., Salaun, C., Graham, S. V. and Gray, N. K. (2011) Nuclear relocalisation of cytoplasmic poly(A)-binding proteins PABP1 and PABP4 in response to UV irradiation reveals mRNA-dependent export of metazoan PABPs. Journal of Cell Science, 124(19), pp. 3344-3355. (doi: 10.1242/jcs.087692) (PMID:21940797) (PMCID:PMC3178455)

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Abstract

Poly(A)-binding protein 1 (PABP1) has a fundamental role in the regulation of mRNA translation and stability, both of which are crucial for a wide variety of cellular processes. Although generally a diffuse cytoplasmic protein, it can be found in discrete foci such as stress and neuronal granules. Mammals encode several additional cytoplasmic PABPs that remain poorly characterised, and with the exception of PABP4, appear to be restricted in their expression to a small number of cell types. We have found that PABP4, similarly to PABP1, is a diffusely cytoplasmic protein that can be localised to stress granules. However, UV exposure unexpectedly relocalised both proteins to the nucleus. Nuclear relocalisation of PABPs was accompanied by a reduction in protein synthesis but was not linked to apoptosis. In examining the mechanism of PABP relocalisation, we found that it was related to a change in the distribution of poly(A) RNA within cells. Further investigation revealed that this change in RNA distribution was not affected by PABP knockdown but that perturbations that block mRNA export recapitulate PABP relocalisation. Our results support a model in which nuclear export of PABPs is dependent on ongoing mRNA export, and that a block in this process following UV exposure leads to accumulation of cytoplasmic PABPs in the nucleus. These data also provide mechanistic insight into reports that transcriptional inhibitors and expression of certain viral proteins cause relocation of PABP to the nucleus

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Graham, Professor Sheila and Salaun, Dr Christine
Authors: Burgess, H. M., Richardson, W. A., Anderson, R. C., Salaun, C., Graham, S. V., and Gray, N. K.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Cell Science
Publisher:The Company of Biologists Ltd.
ISSN:0021-9533
ISSN (Online):1477-9137

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
251281A Multifunctional Regulatory Pprotein Conserved throughout the Herpesvirus FamilyJ ClementsMedical Research Council (MRC)G9826324Infection Immunity and Inflammation Life Sciences