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The spliced leader (SL) is a small nucleotide sequence (mini-exon) that is required for protein-coding gene expression. The SL is encoded as part of a donor RNA gene (SL RNA) and transferred to pre-mRNA during trans-splicing to generate the mature 5′ ends of mRNAs ( Trans-Splicing, Fig. 1). SL addition is unique to kinetoplastids, euglenoids, nematodes, and flatworms. In kinetoplastids, it serves to resolve polycistronic into translatable monocistronic transcripts and may have the same function in helminths. SL RNA in Trypanosoma brucei is 140 nucleotides long and is encoded by about 200 genes organized in tandem repeats of 1.35 kb. SL sequences have similar structures in different organisms and resemble small nuclear RNAs (snRNAs) but vary in length among different species. In kinetoplastids, every nuclear-derived mRNA carries a 39–41 SL nucleotide sequence at its 5′ terminus, while helminth SLs are 22 and 36 nucleotides long, respectively.