Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs..pdf (2.82 MB)
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Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs

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journal contribution
posted on 23.02.2016, 12:22 by H. A. King, L. C. Cobbold, X. Pichon, T. Pöyry, L. A. Wilson, H. Booden, R. Jukes-Jones, K. Cain, K. S. Lilley, Martin David Bushell, A. E. Willis
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.

History

Citation

Cell Death and Differentiation, 2014, 21 (1), pp. 161-171

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Molecular & Cell Biology

Version

VoR (Version of Record)

Published in

Cell Death and Differentiation

Publisher

Nature Publishing Group for Congregazione dei Figli dell'Immacolata Concezione (CFIC), Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Dermopatico dell'Immacolata (IDI-IRCCS)

issn

1350-9047

eissn

1476-5403

Acceptance date

30/08/2013

Copyright date

2014

Available date

23/02/2016

Publisher version

http://www.nature.com/cdd/journal/v21/n1/full/cdd2013135a.html

Language

en