Structural basis of step II spliced leader RNA trans-splicing in trypanosomatid parasites
In the authors' words
Messenger RNA (mRNA) synthesis is fundamental to eukaryotic gene expression. In kinetoplastid parasites, including the human pathogens Trypanosoma and Leishmania, mRNAs are produced through a mechanism called Spliced Leader (SL) RNA trans-splicing. In this process, a short SL exon from a small noncoding RNA is joined to the 5' end of every mRNA, ensuring transcript stability and translation. Despite decades of study, the structural and mechanistic basis of SL trans-splicing remains elusive. Here, we report cryogenic electron microscopy structures of step II SL trans-splicing machineries from Leishmania tarentolae. These structures reveal the molecular mechanism of SL exon ligation and uncover lineage-specific adaptations that remodel the trypanosomatid trans-spliceosome for SL trans-splicing while preserving fundamental spliceosomal chemistry. Altogether, our results establish a mechanistic framework for SL trans-splicing and illuminate the evolutionary diversification of RNA processing in deeply diverged eukaryotes.
Appeared: Friday, September 25. Nature Communications. Peer-reviewed journal.