Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Elucidating the role of termination-based feedback mechanisms in mRNA translation in yeast
J Krishnan

Last modified: 2014-03-31


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, as well as its interplay with other regulatory mechanisms.

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 (at different locations) 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 translation systems.

In this talk we will discuss a mathematical modelling framework aimed at elucidating the role of this feedback regulation,  its interaction with tRNA which mediates premature stop codon readthrough. We will build on this to investigate the effect of the  nonsense-mediated decay mRNA surveillance mechanism in this setting.

 The translation process is modelled at multiple levels of detail and using multiple formalisms, and the effects of the regulatory mechanisms are systematically  elucidated therein.We then show that the essential predictions of the in-silico approach are matched by experiments. If time permits, we will discuss other related feedback mechanisms involving translation termination

 This work is done in collaboration with Eric de Silva, Yun-Bo Zhao, Russell Betney and Ian Stansfield.