Trans -Splicing in Trypanosomes: Machinery and Its Impact on the Parasite Transcriptome

In trypanosomes, all RNAs are processed by the concerted action of trans-splicing and polyadenylation. In trans-splicing, a common spliced leader (SL) is donated to all mRNAs from a small RNA molecule, the SL RNA. This article summarizes recent findings in the field focusing on SL RNA transcription, cap modifications and pseudouridylation. The role(s) of these modifications for splicing and gene expression are discussed. The recruitment of SL RNA to the spliceosome depends on splicing factors and recent progress in identifying such factors is described. A recent major advance in understanding the role of trans-splicing in the trypanosome transcriptome was obtained by whole-genome mapping of the SL and polyadenylation sites, revealing surprising heterogeneity and suggesting that gene regulation, especially during cycling between the two hosts of the parasite, involves alternative trans-splicing. Finally, the SL silencing mechanism, which is harnessed by the parasite to control gene expression under stress, is discussed.