Recursive splicing in insects and vertebrates

The mechanisms by which the very longest genes in eukaryotic genomes are accurately processed are poorly understood. It was thought that intron removal generally involved a single excisive step. Later studies showed that, in flies, some introns contain internal splice sites that cause ‘recursive splicing’, in which single introns are removed ‘bit-by-bit’ in several sequential splicing reactions. Brenton Graveley and coworkers demonstrate that the scope of this regulatory mechanism is much more extensive in flies than had been appreciated. They identify nearly 200 zero-nucleotide exons in Drosophila that are the products of recursive splicing. Jernej Ule and colleagues identify recursive splicing sites in vertebrates, particularly within long genes encoding proteins that are involved in neuronal development. Analysis of the mechanism of their splicing reveals that such splicing sites can be used to dictate different mRNA isoforms.