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Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs
Post-transcriptional control of gene expression is mediated by the interaction of RNA-binding proteins with their cognate mRNAs that specifically regulate their stability, localization and translation. mRNA-binding proteins are multifunctional and it has been proposed therefore that a combinatorial...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857619/ https://www.ncbi.nlm.nih.gov/pubmed/24141718 http://dx.doi.org/10.1038/cdd.2013.135 |
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author | King, H A Cobbold, L C Pichon, X Pöyry, T Wilson, L A Booden, H Jukes-Jones, R Cain, K Lilley, K S Bushell, M Willis, A E |
author_facet | King, H A Cobbold, L C Pichon, X Pöyry, T Wilson, L A Booden, H Jukes-Jones, R Cain, K Lilley, K S Bushell, M Willis, A E |
author_sort | King, H A |
collection | PubMed |
description | Post-transcriptional control of gene expression is mediated by the interaction of RNA-binding proteins with their cognate mRNAs that specifically regulate their stability, localization and translation. mRNA-binding proteins are multifunctional and it has been proposed therefore that a combinatorial RNA-binding protein code exists that allows specific protein sub-complexes to control cytoplasmic gene expression under a range of pathophysiological conditions. We show that polypyrimidine tract-binding protein (PTB) is central to one such complex that forms in apoptotic cells. Thus, during apoptosis initiated by TNF-related apoptosis inducing ligand there is a change in the repertoire of RNA-binding proteins with which PTB interacts. We show that altering the cellular levels of PTB and its binding partners, either singly or in combination, is sufficient to directly change the rates of apoptosis with increased expression of PTB, YBX1, PSF and NONO/p54(nrb) accelerating this process. Mechanistically, we show that these proteins post-transcriptionally regulate gene expression, and therefore apoptotic rates, by interacting with and stimulating the activity of RNA elements (internal ribosome entry segments) found in mRNAs that are translated during apoptosis. Taken together, our data show that PTB function is controlled by a set of co-recruited proteins and importantly provide further evidence that it is possible to dictate cell fate by modulating cytoplasmic gene expression pathways alone. |
format | Online Article Text |
id | pubmed-3857619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-38576192014-01-01 Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs King, H A Cobbold, L C Pichon, X Pöyry, T Wilson, L A Booden, H Jukes-Jones, R Cain, K Lilley, K S Bushell, M Willis, A E Cell Death Differ Original Paper Post-transcriptional control of gene expression is mediated by the interaction of RNA-binding proteins with their cognate mRNAs that specifically regulate their stability, localization and translation. mRNA-binding proteins are multifunctional and it has been proposed therefore that a combinatorial RNA-binding protein code exists that allows specific protein sub-complexes to control cytoplasmic gene expression under a range of pathophysiological conditions. We show that polypyrimidine tract-binding protein (PTB) is central to one such complex that forms in apoptotic cells. Thus, during apoptosis initiated by TNF-related apoptosis inducing ligand there is a change in the repertoire of RNA-binding proteins with which PTB interacts. We show that altering the cellular levels of PTB and its binding partners, either singly or in combination, is sufficient to directly change the rates of apoptosis with increased expression of PTB, YBX1, PSF and NONO/p54(nrb) accelerating this process. Mechanistically, we show that these proteins post-transcriptionally regulate gene expression, and therefore apoptotic rates, by interacting with and stimulating the activity of RNA elements (internal ribosome entry segments) found in mRNAs that are translated during apoptosis. Taken together, our data show that PTB function is controlled by a set of co-recruited proteins and importantly provide further evidence that it is possible to dictate cell fate by modulating cytoplasmic gene expression pathways alone. Nature Publishing Group 2014-01 2013-10-18 /pmc/articles/PMC3857619/ /pubmed/24141718 http://dx.doi.org/10.1038/cdd.2013.135 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Original Paper King, H A Cobbold, L C Pichon, X Pöyry, T Wilson, L A Booden, H Jukes-Jones, R Cain, K Lilley, K S Bushell, M Willis, A E Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs |
title | Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs |
title_full | Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs |
title_fullStr | Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs |
title_full_unstemmed | Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs |
title_short | Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs |
title_sort | remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular iress |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857619/ https://www.ncbi.nlm.nih.gov/pubmed/24141718 http://dx.doi.org/10.1038/cdd.2013.135 |
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