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Mathematical modelling of translation of mRNA in eucaryotes; steady states, time-dependent processes and application to reticulocytest

Abstract

Based on a kinetic model for the translation of mRNA the following conclusions are derived:

(1) Under normal conditions in a cell, initiation and elongation determine the rate of protein synthesis. The latter process turns out to be potentially even more important than the former. Termination does not influence the rate of protein synthesis.

(2) Ribosomes are distributed nearly uniformly along mRNAs owing to the relatively fast termination under physiological conditions.

(3) The limited supply of free ribosomes in most cells prevents piling up of ribosomes on mRNAs by changes in the translational system alone.

(4) The relaxation time of the translation system is short. In reticulocytes a new steady state is reached after about 200 s following a perturbation.

(5) Lodish's hypothesis (Lodish, 1974) that the translation of the less efficient mRNA-species is stimulated preferentially by an unspecific stimulation of the overall initiation is supported by the analysis of a detailed model of translation in reticulocytes. The previously given explanation for this effect has, however, been revised. It is shown that the "unspecific stimulation" can lead to greatly differing effects; changes of the mRNA-eIF 4B-interaction influence the a- to β-globin ratio to a much greater extent than do changes in the activation process of the 40S subunits.


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