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Large-scale mRNA translation and the intricate effects of competition for the finite pool of ribosomes

Titelangaben

Jain, Aditi ; Margaliot, Michael ; Gupta, Arvind Kumar:
Large-scale mRNA translation and the intricate effects of competition for the finite pool of ribosomes.
In: Interface : Journal of the Royal Society. Bd. 19 (2022) Heft 188 . - 20220033.
ISSN 1742-5662
DOI: https://doi.org/10.1098/rsif.2022.0033

Rez.:

Angaben zu Projekten

Projektfinanzierung: Andere
Israeli Science Foundation (ISF), Research grant
DST-SERB, Government of India (grants CRG/2019/004669, MTR/2019/000312)

Abstract

We present a new theoretical framework for large-scale mRNA translation using a network of models called the ribosome flow model with Langmuir kinetics (RFMLK), interconnected via a pool of free ribosomes. The input to each RFMLK depends on the pool density, and it affects the initiation rate and potentially also the internal ribosome entry rates along each RFMLK. Ribosomes that detach from an RFMLK owing to termination or premature drop-off are fed back into the pool. We prove that the network always converges to a steady state, and study its sensitivity to variations in the parameters. For example, we show that if the drop-off rate at some site in some RFMLK is increased then the pool density increases and consequently the steady-state production rate in all the *other* RFMLKs increases. Surprisingly, we also show that modifying a parameter of a certain RFMLK can lead to arbitrary effects on the densities along the modified RFMLK, depending on the parameters in the entire network. We conclude that the competition for shared resources generates an indirect and intricate web of mutual effects between the mRNA molecules that must be accounted for in any analysis of translation.

Weitere Angaben

Publikationsform: Artikel in einer Zeitschrift
Begutachteter Beitrag: Ja
Keywords: mathematical modelling of competition for shared resources; ribosome drop-off; internal ribosome entry sites; cooperative dynamical systems; entrainment; context dependence in mRNA translation
Institutionen der Universität: Fakultäten > Fakultät für Mathematik, Physik und Informatik > Mathematisches Institut > Lehrstuhl Mathematik V (Angewandte Mathematik)
Profilfelder > Advanced Fields > Nichtlineare Dynamik
Forschungseinrichtungen > Zentrale wissenschaftliche Einrichtungen > Bayreuther Zentrum für Modellierung und Simulation (MODUS)
Titel an der UBT entstanden: Nein
Themengebiete aus DDC: 500 Naturwissenschaften und Mathematik > 510 Mathematik
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie
Eingestellt am: 07 Mär 2025 11:14
Letzte Änderung: 07 Mär 2025 11:14
URI: https://eref.uni-bayreuth.de/id/eprint/92616