Poster (Scientific congresses and symposiums)
mRNA translation rate modeling with an extended TASEP incorporating tRNAs modifications
Joiret, Marc; Rapino, Francesca; Close, Pierre et al.
2019EMBO Workshop - Protein Synthesis and Translational Control
 

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Keywords :
mRNA; ribosome; elongation rate; TASEP; electrostatic interaction; ribosome exit tunnel; codon usage; tRNA modifications; Ribo-Seq; bioinformatics; computational biology
Abstract :
[en] 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.
Research center :
Biomech research Unit - GIGA Institute GIGA In silico medicine
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Joiret, Marc  ;  Université de Liège - ULiège > In silico medecine-Biomechanics Research Unit
Rapino, Francesca  ;  Université de Liège - ULiège > Stem Cells-Cancer Signaling
Close, Pierre  ;  Université de Liège - ULiège > Stem Cells-Cancer Signaling
Geris, Liesbet  ;  Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique
Language :
English
Title :
mRNA translation rate modeling with an extended TASEP incorporating tRNAs modifications
Publication date :
05 September 2019
Number of pages :
A0
Event name :
EMBO Workshop - Protein Synthesis and Translational Control
Event organizer :
European Molecular Biology Organization
Event place :
Heidelberg, Germany
Event date :
from 04-09-2019 to 07-09-2019
By request :
Yes
Audience :
International
European Projects :
H2020 - 772418 - INSITE - Development and use of an integrated in silico-in vitro mesofluidics system for tissue engineering
Name of the research project :
Joint-t-against-Osteoarthritis; EOS grant n° 30480119; ERC grant agreement n°772418 (INSITE)
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen [BE]
CER - Conseil Européen de la Recherche [BE]
CE - Commission Européenne [BE]
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since 11 October 2019

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