title: Nuclear relocalisation of cytoplasmic poly(A)-binding proteins PABP1 and PABP4 in response to UV irradiation reveals mRNA-dependent export of metazoan PABPs.
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.
authors.affiliation: MRC Centre for Reproductive Health/MRC Human Reproductive Sciences Unit, Queens Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Burgess
authors.forename: William A
authors.initials: WA
authors.lastname: Richardson
authors.forename: Ross C
authors.initials: RC
authors.lastname: Anderson
authors.forename: Christine
authors.initials: C
authors.lastname: Salaun
authors.forename: Sheila V
authors.initials: SV
authors.lastname: Graham
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Gray
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001798:Blood Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D039122:Poly(A)-Binding Protein I / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D021381:Protein Transport / Q000528:radiation effects*; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014466:Ultraviolet Rays
chemical_list: D001798:Blood Proteins; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; C104581:PABPC4 protein, human; D039122:Poly(A)-Binding Protein I; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins