John Libbey Eurotext

Bulletin du Cancer


Pre-mRNA alternative splicing in cancer: functional impact, molecular mechanisms and therapeutic perspectives Volume 93, issue 9, Septembre 2006


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Groupe ARN, Département de microbiologie et d’infectiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4

For most of the 25 000 human genes, the removal of introns by pre-messenger RNA splicing represents an essential step towards the production of functional messenger RNAs. Moreover, a majority of pre-messenger RNAs is alternatively spliced to yield different messenger RNAs. Cancer cells often display aberrant profiles of alternative splicing producing isoforms that can stimulate cell proliferation and migration or improve resistance to apoptosis. While mutations at splice sites or in splicing control elements have been identified, changes are also caused by alterations in the expression of proteins that affect splice site selection. Current challenges consist in documenting the functional diversity generated by alternative splicing and its contribution to different types of cancers. The development of innovative approaches aimed at reprogramming alternative splicing offers promising perspectives in cancer therapy.