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
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