Sualization tool Genesis is available at http://genome. tugraz.at/genesisclient/genesisclient_description.shtml). 
On the basis of the more general analysis (Figure 3B), we found suppressors 
associated with gamma-Tubulin related molecular functions, mitosis and transcription. Enhancers seemed associatedwith various enzymatic activities and RNA localization, whereas the group of lethal candidates showed diverse immune-responsive functions (regulation of stress-activated protein kinase, RNase complex etc.). The detailed term-by-term analysis of combinations of candidate groups revealed that phenotypic suppressors (categories 1+2) confirmed these findings. On the contrary, enhancers showed relatively weak associations, with the exception of particularly strong enhancers (category 6), which were enriched for RNA localization-related GO terms. The strongest degree of enrichment, however, could be seen for the class of lethal genes (category 7) that showed significant values for many different GO terms, ranging from RNA metabolism and localization to not further specified nuclear functions. The ontology-weighted approach allowed drilling deeper into the GO 79983-71-4 hierarchy and identifying further functional groups that seem relevant in polyQmediated toxicity. Here, enhancers were associated e.g. with axonal growth cone development and splicing-related activities, whereas suppressors showed additional involvement in SH2domain MedChemExpress Docosahexaenoyl ethanolamide binding and therefore possibly signal transduction. Again, a very strong degree of GO enrichment was found for the group of lethal genes, with nonsense-mediated decay being one of the strongest terms. Overall, these provide several interesting entry points for further investigations into polyQ-mediated toxicity.Modifiers of Polyglutamine ToxicityTable 1. List of unspecific modifiers of polyQ-induced toxicity.Name/CG Rab30/CG9100 Aats-his/CG6335 MED14/CG12031 Prp8/CG8877 Nelf-E/CG5994 RpS10a/CG12275 -/CG11985 Prosbeta2/CG3329 Rpn9/CG10230 bic/CG3644 MRG15/CG6363 Hop/CG2720 -/CG6364 -/CG6873 Nrx-IV/CGEffect on Tau-induced REP E E E E E E E E E E S S E E EEffect on polyQ-induced REP E E E E E E E E E E S S E E EPredicted molecular function/biological process (as listed on flybase.org) GTPase activity/involved in vesicle sorting and transport histidine-tRNA ligase/histidyl-tRNA aminoacylation protein binding/transcription from RNA polymerase II promoter unknown/nuclear mRNA splicing, via spliceosome mRNA binding/negative regulation of transcription from RNA polymerase II promoter during mitosis Structural constituent of ribosome/neurogenesis unknown/mitotic spindle organization endopeptidase activity/catalytic constituent of the proteasome (betasubunit), protein degradation endopeptidase activity/regulation of exit from mitosis, protein degradation unknown/regulation of establishment of protein localization, RNA binding, intracellular mRNA localization unknown/chromatin silencing unfolded protein binding/protein folding Uridine kinase activity/phagocytosis, engulfment Actin binding, polymerization/neurogenesis transmembrane signaling receptor activity/dorsal closure; nerve maturation; regulation of tube size, open tracheal system; establishment 1313429 of glial blood-brain barrier; septate junction assembly; axon ensheathment. cyclin-dependent protein kinase regulator activity/mitotic cell cycle, embryonic; mitosis unknown/neurogenesis unknown/cytokinesesis zinc ion binding/unknown peptide alpha-N-acetyltransferase activity/oogenesis, neurog.Sualization tool Genesis is available at http://genome. tugraz.at/genesisclient/genesisclient_description.shtml). On the basis of the more general analysis (Figure 3B), we found suppressors associated with gamma-Tubulin related molecular functions, mitosis and transcription. Enhancers seemed associatedwith various enzymatic activities and RNA localization, whereas the group of lethal candidates showed diverse immune-responsive functions (regulation of stress-activated protein kinase, RNase complex etc.). The detailed term-by-term analysis of combinations of candidate groups revealed that phenotypic suppressors (categories 1+2) confirmed these findings. On the contrary, enhancers showed relatively weak associations, with the exception of particularly strong enhancers (category 6), which were enriched for RNA localization-related GO terms. The strongest degree of enrichment, however, could be seen for the class of lethal genes (category 7) that showed significant values for many different GO terms, ranging from RNA metabolism and localization to not further specified nuclear functions. The ontology-weighted approach allowed drilling deeper into the GO hierarchy and identifying further functional groups that seem relevant in polyQmediated toxicity. Here, enhancers were associated e.g. with axonal growth cone development and splicing-related activities, whereas suppressors showed additional involvement in SH2domain binding and therefore possibly signal transduction. Again, a very strong degree of GO enrichment was found for the group of lethal genes, with nonsense-mediated decay being one of the strongest terms. Overall, these provide several interesting entry points for further investigations into polyQ-mediated toxicity.Modifiers of Polyglutamine ToxicityTable 1. List of unspecific modifiers of polyQ-induced toxicity.Name/CG Rab30/CG9100 Aats-his/CG6335 MED14/CG12031 Prp8/CG8877 Nelf-E/CG5994 RpS10a/CG12275 -/CG11985 Prosbeta2/CG3329 Rpn9/CG10230 bic/CG3644 MRG15/CG6363 Hop/CG2720 -/CG6364 -/CG6873 Nrx-IV/CGEffect on Tau-induced REP E E E E E E E E E E S S E E EEffect on polyQ-induced REP E E E E E E E E E E S S E E EPredicted molecular function/biological process (as listed on flybase.org) GTPase activity/involved in vesicle sorting and transport histidine-tRNA ligase/histidyl-tRNA aminoacylation protein binding/transcription from RNA polymerase II promoter unknown/nuclear mRNA splicing, via spliceosome mRNA binding/negative regulation of transcription from RNA polymerase II promoter during mitosis Structural constituent of ribosome/neurogenesis unknown/mitotic spindle organization endopeptidase activity/catalytic constituent of the proteasome (betasubunit), protein degradation endopeptidase activity/regulation of exit from mitosis, protein degradation unknown/regulation of establishment of protein localization, RNA binding, intracellular mRNA localization unknown/chromatin silencing unfolded protein binding/protein folding Uridine kinase activity/phagocytosis, engulfment Actin binding, polymerization/neurogenesis transmembrane signaling receptor activity/dorsal closure; nerve maturation; regulation of tube size, open tracheal system; establishment 1313429 of glial blood-brain barrier; septate junction assembly; axon ensheathment. cyclin-dependent protein kinase regulator activity/mitotic cell cycle, embryonic; mitosis unknown/neurogenesis unknown/cytokinesesis zinc ion binding/unknown peptide alpha-N-acetyltransferase activity/oogenesis, neurog.
