Persistent infection with cancer risk-related viruses leads to molecular, cellular and immune response changes in host organisms that in some cases direct cellular transformation. Alternative splicing is a conserved cellular process that increases the coding complexity of genomes at the pre-mRNA processing stage. Human and other animal tumour viruses use alternative splicing as a process to maximize their transcriptomes and proteomes. Medical therapeutics to clear persistent viral infections are still limited. However, specific lessons learned in some viruses [e.g. HIV and HCV (hepatitis C virus)] suggest that drug-directed inhibition of alternative splicing could be useful for this purpose. The present review describes the basic mechanisms of constitutive and alternative splicing in a cellular context and known splicing patterns and the mechanisms by which these might be achieved for the major human infective tumour viruses. The roles of splicing-related proteins expressed by these viruses in cellular and viral gene regulation are explored. Moreover, we discuss some currently available drugs targeting SR (serine/arginine-rich) proteins that are the main regulators of constitutive and alternative splicing, and their potential use in treatment for so-called persistent viral infections.
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July 2012
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Review Article|
June 27 2012
Alternative splicing in human tumour viruses: a therapeutic target?
Hegel R. Hernandez-Lopez;
Hegel R. Hernandez-Lopez
1Centre for Virus Research, Institute of Infection Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, Scotland, U.K.
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Sheila V. Graham
Sheila V. Graham
1
1Centre for Virus Research, Institute of Infection Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, Scotland, U.K.
1To whom correspondence should be addressed (email sheila.graham@glasgow.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 08 2012
Revision Received:
April 27 2012
Accepted:
May 03 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 445 (2): 145–156.
Article history
Received:
March 08 2012
Revision Received:
April 27 2012
Accepted:
May 03 2012
Citation
Hegel R. Hernandez-Lopez, Sheila V. Graham; Alternative splicing in human tumour viruses: a therapeutic target?. Biochem J 15 July 2012; 445 (2): 145–156. doi: https://doi.org/10.1042/BJ20120413
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