Nuclear relocalisation of cytoplasmic poly(A)-binding proteins PABP1 and PABP4 in response to UV irradiation reveals mRNA-dependent export of metazoan PABPs
Autor: | Ross C. Anderson, Sheila V. Graham, William A. Richardson, Hannah M. Burgess, Christine Salaün, Nicola K. Gray |
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Rok vydání: | 2011 |
Předmět: |
ICP27
Cytoplasm Ultraviolet Rays Active Transport Cell Nucleus Apoptosis Cytoplasmic Granules Poly(A)-Binding Protein I Poly(A)-Binding Proteins RNA Transport Cellular stress response Immediate early protein Immediate-Early Proteins Mice 03 medical and health sciences Stress granule Poly(A)-binding protein PABPC4 medicine Protein biosynthesis Animals Humans RNA Messenger Nuclear export signal Research Articles 030304 developmental biology Cell Nucleus 0303 health sciences biology Translational reprogramming 030302 biochemistry & molecular biology Blood Proteins Cell Biology Translation initiation factor Recombinant Proteins Transport protein Cell biology Protein Transport Cell nucleus medicine.anatomical_structure Microscopy Fluorescence Protein Biosynthesis Subcellular localisation NIH 3T3 Cells biology.protein HeLa Cells |
Zdroj: | Burgess, H M, Richardson, W A, Anderson, R C, Salaun, C, Graham, S V & 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, vol. 124, no. 19, pp. 3344-3355 . https://doi.org/10.1242/jcs.087692 Journal of Cell Science |
ISSN: | 1477-9137 0021-9533 |
Popis: | 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. |
Databáze: | OpenAIRE |
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