Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs

King, H.A. et al. (2014) Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs. Cell Death and Differentiation, 21(1), pp. 161-171. (doi: 10.1038/cdd.2013.135) (PMID:24141718) (PMCID:PMC3857619)

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Abstract

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/p54nrb 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bushell, Professor Martin
Authors: 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., and Willis, A.E.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cell Death and Differentiation
Publisher:Springer Nature
ISSN:1350-9047
ISSN (Online):1476-5403
Published Online:18 October 2013
Copyright Holders:Copyright © 2014 Macmillan Publishers Limited
First Published:First published in Cell Death and Differentiation 21(1): 161-171
Publisher Policy:Reproduced under a Creative Commons License

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