A global genetic analysis of nematode spliced-leader trans-splicing Jonathan Pettitt Berndt Mueller Bernadette Connolly.

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A global genetic analysis of nematode spliced-leader trans-splicing Jonathan Pettitt Berndt Mueller Bernadette Connolly

Spliced-leader trans-splicing ‘Slintron’

Taxonomic Distribution of SL trans-splicing

Origin of Spliced-Leader trans-splicing C. elegans SL1 RNA U1 snRNA TMG SM

SL trans-splicing in C. elegans 70% of C. elegans genes are SL1 trans-spliced Loss of SL1 RNA gene is embryonic lethal Many questions remain – how are trans-splicing and cis-splicing coordinated in the same cell? – How is the SL RNA brought to the 5’end of the mRNA? – How are SM proteins recycled from the SL introns?

An in vivo assay for SL trans-splicing GFP SL1 GFP ATG outron SL trans-splicing

Screening for molecules required for SL trans-splicing GFP ATG outron Control mRNA

Candidate RNAi Screens

Summary Developed in vivo assay to visualise defects in SL trans-splicing First ever systematic genetic screens for molecules required for SL trans-splicing in any organism SL trans-splicing an ideal target for the development of novel anti-helminthics: – Not present in plants or vertebrates