Evolution and function of mRNA 5'spliced leader (SL) trans-splicing

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The goal of this research is to understand the evolution and function of an important but imperfectly-understood gene expression mechanism - SL trans-splicing. SL trans-splicing is a form of RNA splicing, which is an important step in the expression of most genes in complex organisms or cells. However, unlike conventional RNA splicing, which cuts out segments from a single RNA molecule and joins them back together, in trans-splicing segments of two entirely independent RNA molecules are joined together. Conventional RNA splicing is universal among complex organisms, but SL trans-splicing, though widespread, is not found in every group. The distribution indicates that SL trans-splicing either arose independently several times during evolution, or it has been lost several different times. One of the goals of this research program is to determine which of these hypothetical scenarios is correct. These studies will be focussed on the major branch of the animals that includes humans, because, although humans and other higher vertebrates do not carry out SL trans-splicing, we recently discovered that SL trans-splicing does occur in our closest non-vertebrate chordate relatives, the tunicates. We will assess the distribution of SL trans-splicing among the major groups of vertebrates/chordates, and also in several other phyla that, along with the chordates, make up the major animal division termed the deuterostomes. The results will enable us to determine whether SL trans-splicing arose within the tunicates, or was lost within the vertebrates. We will also carry out experimental studies in tunicates to clarify the genetic functions of trans-splicing in the chordates. The information from this research will provide useful insight into the evolutionary dynamics of gene expression mechanisms and on the impact of evolutionary change in gene expression mechanisms on the evolution of the genome.