Modeling Eukaryotic Translation Initiation Based on TCP-seq

Background: Translation regulation and specifically its initiation step is a fundamental to gene expression control. Nevertheless, various aspects related to the biophysics of translation initiation are currently not well understood or modeled.

Methods: A novel protocol named Translation Complex Profile Sequencing (TCP-seq) was developed and implement on S. cerevisiae. This protocol provides the footprints of the small subunit (SSU) of the ribosome (possibly with additional factors) across the entire transcriptome of the analyzed organism at a resolution of single nucleotides. In this study, based the TCP-seq data we develop for the first-time quantitative model related to the affect of transcript features on the dynamic of the SSU and on protein levels. Among other our model is based novel tools for detecting complex statistical relations between variables such as the Maximal Information Coefficient.

Results: Several important features along the transcript were recognized to affect the dynamic of the SSU, such as the context of AUG sub-sequences and local mRNA folding energy. A predictive biophysics model of the translation initiation process in eukaryotes is being developed.

Conclusions: Based on the TCP-seq data we can reveal features in the transcript that affect the scanning of the SSU, and as a result affect the initiation step, allowing better understanding, modeling, and engineering of translation initiation in eukaryotes.