Mature mRNA 3' end formation stimulates RNA export from the nucleus

We have analysed nucleocytoplasmic export of mRNAs in primate cells with the aim of identifying signals promoting RNA transport. Our results demonstrate that sequences directing either histone mRNA 3' processing or cleavage/polyadenylation of mRNA stimulate nucleocytoplasmic RNA transport. To elucidate the nature of this stimulation, we engineered test gene transcripts which could obtain a mature histone 3' end by the RNA cleaving activity of a cis-acting ribozyme, thus circumventing the cellular 3' end processing machinery. However, such transcripts were found to be transport deficient and accumulated in the nuclear compartment. Our experiments provide genetic evidence that there is a linkage between 3' end formation and the export of RNA transcripts from the nucleus. Analysis of a similar series of histone mRNAs in which the mature 3' end was generated by means of ribozyme cleavage led to the discovery of a second export mechanism which relies on features specific for mature histone RNA and which can be uncoupled from the cellular processing machinery. The presence of histone mRNA sequences and of the highly conserved histone hairpin structure, positioned close to the 3' terminus, are critical determinants for this export mechanism.