mRNA/protein sequence complementarity and its determinants: The impact of affinity scales.

PLoS Computational Biology
Lukas Bartonek, Bojan Zagrovic

Abstract

It has recently been demonstrated that the nucleobase-density profiles of mRNA coding sequences are related in a complementary manner to the nucleobase-affinity profiles of their cognate protein sequences. Based on this, it has been proposed that cognate mRNA/protein pairs may bind in a co-aligned manner, especially if unstructured. Here, we study the dependence of mRNA/protein sequence complementarity on the properties of the nucleobase/amino-acid affinity scales used. Specifically, we sample the space of randomly generated scales by employing a Monte Carlo strategy with a fitness function that depends directly on the level of complementarity. For model organisms representing all three domains of life, we show that even short searches reproducibly converge upon highly optimized scales, implying that the topology of the underlying fitness landscape is decidedly funnel-like. Furthermore, the optimized scales, generated without any consideration of the physicochemical attributes of nucleobases or amino acids, resemble closely the nucleobase/amino-acid binding affinity scales obtained from experimental structures of RNA-protein complexes. This provides support for the claim that mRNA/protein sequence complementarity may indeed be ...Continue Reading

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Citations

Jun 1, 2018·FEBS Letters·Bojan ZagrovicAnton A Polyansky
Apr 7, 2019·Journal of Molecular Evolution·Jacques Demongeot, Hervé Seligmann
Mar 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lukas BartonekBojan Zagrovic
Dec 16, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jacques DemongeotHervé Seligmann
Dec 31, 2020·Life·Alexander Nesterov-MuellerHervé Seligmann
Apr 3, 2019·Journal of Theoretical Biology·Jacques Demongeot, Hervé Seligmann
Sep 1, 2021·Proceedings of the National Academy of Sciences of the United States of America·Michael Yarus

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