mRNA translation rate modeling with an extended TASEP incorporating tRNAs modifications

Translational regulation through synonymous codon usage has been recently shown to play an important role in health and disease. Modified tRNAs are important actors involved in regulating protein expression levels by optimizing the decoding of differentially used codons, nevertheless their contribution in protein synthesis dynamics remain unclear. Totally Asymmetric Simple Exclusion Process (TASEP) models have been used to quantify the transcripts translation rate by ribosomes. Our work aims at extending TASEP modeling to accommodate for tRNA modifications effects. We generated a computational stochastic model quantifying protein synthesis rates. The algorithm uses ribosome residence time per codon from transcripts codons sequences, relative transcripts abundance and tables of (modified or not) tRNA relative abundance. Important features in the model include the elongation rate variation caused by charged amino-acids in the ribosomal exit tunnel, proline ring opening delay at the peptide transfer center and optionally transcript secondary structure slow down effects. The model allows to compare relative protein expression levels as well as RiboSeq profiles in different scenarios with a controllable pool of ribosomes.
We intend to use our model to help understand how codon usage and tRNA modifications dynamically interact and impact on protein synthesis.