Sequence signatures of direct complementarity between mRNAs and cognate proteins on multiple levels.

Nucleic Acids Research
Mario HlevnjakBojan Zagrovic

Abstract

A potential connection between physico-chemical properties of mRNAs and cognate proteins, with implications concerning both the origin of the genetic code and mRNA-protein interactions, is unexplored. We compare pyrimidine content of naturally occurring mRNA coding sequences with the propensity of cognate protein sequences to interact with pyrimidines. The latter is captured by polar requirement, a measure of solubility of amino acids in aqueous solutions of pyridines, heterocycles closely related to pyrimidines. We find that the higher the pyrimidine content of an mRNA, the stronger the average propensity of its cognate protein's amino acids to interact with pyridines. Moreover, window-averaged pyrimidine profiles of individual mRNAs strongly mirror polar-requirement profiles of cognate protein sequences. For example, 4953 human proteins exhibit a correlation between the two with |R| > 0.8. In other words, pyrimidine-rich mRNA regions quantitatively correspond to regions in cognate proteins containing residues soluble in pyrimidine mimetics and vice versa. Finally, by studying randomized genetic code variants we show that the universal genetic code is highly optimized to preserve these correlations. Overall, our findings redef...Continue Reading

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Citations

Nov 21, 2013·Nature Communications·Anton A PolyanskyBojan Zagrovic
Jul 23, 2013·Nucleic Acids Research·Anton A Polyansky, Bojan Zagrovic
Jul 30, 2015·Physical Chemistry Chemical Physics : PCCP·Matea HajnicBojan Zagrovic
Feb 28, 2014·RNA Biology·Bojan Zagrovic
Feb 28, 2014·RNA Biology·Sahotra Sarkar
Mar 11, 2015·Nucleic Acids Research·Mario Hlevnjak, Bojan Zagrovic
Apr 6, 2017·Bioinformatics·David WeichselbaumAnton A Polyansky
Jul 28, 2017·PLoS Computational Biology·Lukas Bartonek, Bojan Zagrovic
Aug 31, 2017·Annual Review of Genetics·Eugene V Koonin, Artem S Novozhilov
Jun 1, 2018·FEBS Letters·Bojan ZagrovicAnton A Polyansky
Jul 15, 2020·Transcription·Jennifer L BootsRenée Schroeder
Mar 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lukas BartonekBojan Zagrovic
Feb 3, 2021·Open Biology·K A Dill, L Agozzino
Aug 3, 2017·Journal of Chemical Theory and Computation·Anita de RuiterBojan Zagrovic

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Methods Mentioned

BETA
NMR

Software Mentioned

HIT
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IUPred

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