Diagenode

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


Dutertre M, Chakrama FZ, Combe E, Desmet FO, Mortada H, Polay Espinoza M, Gratadou L, Auboeuf D

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.

Tags
Bioruptor
Chromatin Shearing
ChIP-qPCR

Share this article

Published
February, 2014

Source

Events

 See all events

 


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy