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A novel class of alternative 3’-terminal exons is involved in cell-cycle regulation by topoisomerase inhibitors

ABSTRACT: Alternative 3’-terminal exons, which use intronic polyadenylation sites, are generally unconserved and lowly expressed, while the main gene products end in the last exon of genes. In this study, we discover a class of human genes, where 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 down-regulated 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53474 | GEO | 2014/02/04

SECONDARY ACCESSION(S): PRJNA232113

REPOSITORIES: GEO

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A novel class of alternative 3M-bM-^@M-^Y-terminal exons is involved in cell-cycle regulation by topoisomerase inhibitors

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