(699b) Message-RNA Degradation Studies: A Comparison of Different Decay Mechanisms

Living organisms are forced to constantly adapt to ever changing external and internal conditions to guarantee their survival, exploiting a multitude of genetic control strategies to perform their incredibly diverse functions. It is now recognized that post-transcriptional controls such as differential mRNA stability are of fundamental importance. However, control mechanisms relying on differential mRNA stability are not fully understood and there is currently no consensus as to how the decay mechanism occurs at a molecular level.

We develop here three mechanistic models of translation that include mRNA degradation, one for each of the three main mechanisms proposed for mRNA decay. Our mathematical models have a compartmental structure in which an mRNA template switches from one compartment to the next following the several stages of degradation. The three mathematical models account for the dynamics of the mRNA degrading enzymes and for the protection that ribosomes confer to the templates by their coverage of the chains.

We applied our models to the lacZ system in E. coli to carry out various computational studies and used experimental data to guide the parameterization of the three models. Our studies show the dependance of the mRNA half life on: (i) ribosomal density on the messages, and (ii) the kinetic rate parameters of the enzyme binding and cleaving of the templates.