Courtesy of Sue Strome (SStrome@aol.com).

Think of mRNA splicing and the first image that comes to mind is the process of snipping out the non-coding segments from a pre-mRNA, allowing exons to be strung together into a mature message. Indeed, cis-splicing events occur in most mRNAs in vertebrate cells. But not all exons derive from their pre-mRNA — in many organisms, exons from different RNA molecules fuse to form a mature message, in a process called trans-splicing. A rare form of trans-splicing, called spliced leader (SL) trans-splicing, has been reported only in several protists and in less-advanced animal lineages. Now, Vandenberghe et al. provide evidence of SL trans-splicing in a primitive chordate, Ciona intestinalis , raising the possibility that this process also occurs in vertebrates.

Trans-splicing isn't an easy phenomenon to spot, and most stumble on it by accident. This study is no exception. The researchers' original intention was to isolate the gene for the muscle protein troponin I (TnI) in the ascidian C. intestinalis. In doing so, they found that the first 16 nucleotides of the TnI mRNA were nearly identical in sequence to those of at least six other, functionally unrelated mRNAs.

Could the 16-nucleotide stretch be a common exon (the spliced leader) that is spliced onto the 5′ end of distinct acceptor RNAs? If so, then this would be the first example of SL trans-splicing in a chordate. That this was the case was confirmed by the absence of the 16 bases from the TnI genomic sequence and by the trans-splicing of the 16 nucleotides onto an artificial mRNA substrate that retained the TnI splice acceptor site. The authors also identified a strong candidate for the splice donor molecule — a 46-nucleotide RNA species — from which the 16 bases derive.

This discovery of SL trans-splicing in chordates significantly extends the phylogenetic range in which the process is known to occur. Although opinions are divided as to the advantages of trans-splicing, knowing its phylogenetic distribution provides clues about how trans- and cis-splicing have evolved. These two processes might be closely related, as shown by the use of the same consensus splice acceptor/donor sites and the similarity between the SL RNA and a spliceosomal snRNA. But does SL trans-splicing occur in vertebrates? The answer might require some more serendipity.