(620h) Elucidating the Effect of Feedback Control in Translation Termination in Yeast

While feedback regulation has been widely studied in the context of transcription, feedback regulatory effects in translation have been much less studied. In this talk we will discuss modelling efforts aimed at understanding the feedback control structure involving translation termination in yeast, performed in collaboration with experimentalists.  mRNA translation involves roughly three distinct stages, initiation,  elongation and termination.Translation resulting in the synthesis of the release factor protein eRF1, involves this protein participating in its own termination. Experimentally introducing an artificial stop codon in the mRNA leads to the possibility of premature termination leading to a truncated protein being synthesized. Thus in this case the release factor negatively regulates its synthesis  by its action on the premature stop codon.  A very similar feedback regulation in translation is also seen in other systemsIn this talk we will discuss a mathematical modelling framework aimed at elucidating the role of this feedback regulation, and its interaction with tRNA whichmediates premature stop codon readthrough.  The translation process is modelled at multiple levels of detail, and the effects of this feedback regulation is systematically elucidated. The dynamical effects of the feedback and its interplay with other steps in the translation process are elucidated using in-silico analysis. We then show that the essential predictions of the in-silico approach are matched by experiments. This work is done in collaboration with Eric de Silva, Russell Betney and Ian Stansfield.