Deciphering 3′ss Selection in the Yeast Genome Reveals an RNA Thermosensor that Mediates Alternative Splicing

SummaryPoor understanding of the spliceosomal mechanisms to select intronic 3′ ends (3′ss) is a major obstacle to deciphering eukaryotic genomes. Here, we discern the rules for global 3′ss selection in yeast. We show that, in contrast to the uniformity of yeast splicing, the spliceosome uses all available 3′ss within a distance window from the intronic branch site (BS), and that in ∼70% of all possible 3′ss this is likely to be mediated by pre-mRNA structures. Our results reveal that one of these RNA folds acts as an RNA thermosensor, modulating alternative splicing in response to heat shock by controlling alternate 3′ss availability. Thus, our data point to a deeper role for the pre-mRNA in the control of its own fate, and to a simple mechanism for some alternative splicing.

▸ Yeast introns have a diverse range of branch-site (BS) to 3′ splice site (ss) regions ▸ The yeast spliceosome can use all 3′ss inside a sequence range ▸ RNA structure in the BS-3′ss region plays a critical role in defining the proper 3′ss ▸ The APE2 RNA structure in this region is a thermosensor mediating alternate 3′ss choice