Fig 7. Relationship between trans splicing inhibition and methylation changes.

A) Trypanosomes were incubated with 10x EC₅₀ of various compounds for 2h, then splicing was assayed as in Fig 4. The % Y structure (relative to the U3 control) is shown. Results are shown for one experiment (experiment 1) with a full compound set and for a second experiment with selected compounds. A time course for the second experiment is shown in S4A Fig. B) The mean increase in SAM and MTA after treatment with each compound is plotted on the y-axis; the x-axis shows mean and standard deviation of the % Y-structure remaining (data for experiment 1 in (A)). The AN numbers are colour-coded to indicate the time of incubation prior to metabolome analysis. C. Metabolite changes after AN5568 or Act D treatment (both 5h). Each point represents a metabolite; data are in S7 Table. Orange: significantly affected by Actinomycin D; cyan: significantly affected by AN5568; purple: significantly affected by both treatments. Labelled metabolites are: 1- Glutathione disulfide; 2- Lys-Val-Pro; 3- N6,N6,N6-Trimethyl-L-lysine; 4- N6-Acetyl-L-lysine.