A global genetic analysis of nematode spliced-leader trans -splicing

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

description

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. SM. - PowerPoint PPT Presentation

Transcript of A global genetic analysis of nematode spliced-leader trans -splicing

Page 1: A global genetic analysis of nematode  spliced-leader  trans -splicing

A global genetic analysis of nematode spliced-leader trans-splicing

Jonathan PettittBerndt MuellerBernadette Connolly

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Spliced-leader trans-splicing

‘Slintron’

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Taxonomic Distribution of SL trans-splicing

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Origin ofSpliced-Leader trans-splicing

C. elegansSL1 RNA

U1 snRNA

TMG

TMG

SM

SM

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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?

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An in vivo assay for SL trans-splicing

GFPSL1

GFPATG

outron

SL trans-splicing

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Screening for molecules required for SL trans-splicing

GFPATG

outron

Control mRNA

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Candidate RNAi Screens

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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