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

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dc.contributor.author Jain, A.
dc.contributor.author Margaliot, M.
dc.contributor.author Gupta, A.K.
dc.date.accessioned 2022-07-14T21:32:55Z
dc.date.available 2022-07-14T21:32:55Z
dc.date.issued 2022-07-15
dc.identifier.uri http://localhost:8080/xmlui/handle/123456789/3621
dc.description.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. en_US
dc.language.iso en_US en_US
dc.subject context dependence in mRNA translation en_US
dc.subject cooperative dynamical systems en_US
dc.subject entrainment; internal ribosome entry site en_US
dc.subject mathematical modelling of competition for shared resources en_US
dc.subject ribosome drop-off en_US
dc.title Large-scale mRNA translation and the intricate effects of competition for the finite pool of ribosomes en_US
dc.type Article en_US


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