A recently evolved class of alternative 3′-terminal exons involved in cell cycle regulation by topoisomerase inhibitors

Martin Dutertre (), Fatima Zahra Chakrama, Emmanuel Combe, François-Olivier Desmet, Hussein Mortada, Micaela Polay Espinoza, Lise Gratadou and Didier Auboeuf
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Martin Dutertre: INSERM U1052, 28 rue Laennec
Fatima Zahra Chakrama: INSERM U1052, 28 rue Laennec
Emmanuel Combe: INSERM U1052, 28 rue Laennec
François-Olivier Desmet: INSERM U1052, 28 rue Laennec
Hussein Mortada: INSERM U1052, 28 rue Laennec
Micaela Polay Espinoza: INSERM U1052, 28 rue Laennec
Lise Gratadou: INSERM U1052, 28 rue Laennec
Didier Auboeuf: INSERM U1052, 28 rue Laennec

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract Alternative 3′-terminal exons, which use intronic polyadenylation sites, are generally less conserved and expressed at lower levels than the last exon of genes. Here we discover a class of human genes, in which the last exon appeared recently during evolution, and the major gene product uses an alternative 3′-terminal exon corresponding to the ancestral last exon of the gene. This novel class of alternative 3′-terminal exons are downregulated on a large scale by doxorubicin, a cytostatic drug targeting topoisomerase II, and play a role in cell cycle regulation, including centromere–kinetochore assembly. The RNA-binding protein HuR/ELAVL1 is a major regulator of this specific set of alternative 3′-terminal exons. HuR binding to the alternative 3′-terminal exon in the pre-messenger RNA promotes its splicing, and is reduced by topoisomerase inhibitors. These findings provide new insights into the evolution, function and molecular regulation of alternative 3′-terminal exons.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4395

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DOI: 10.1038/ncomms4395

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