Evidence of direct complementary interactions between messenger RNAs and their cognate proteins

Nucleic Acids Research
Anton A Polyansky, Bojan Zagrovic

Abstract

Recently, the ability to interact with messenger RNA (mRNA) has been reported for a number of known RNA-binding proteins, but surprisingly also for different proteins without recognizable RNA binding domains including several transcription factors and metabolic enzymes. Moreover, direct binding to cognate mRNAs has been detected for multiple proteins, thus creating a strong impetus to search for functional significance and basic physico-chemical principles behind such interactions. Here, we derive interaction preferences between amino acids and RNA bases by analyzing binding interfaces in the known 3D structures of protein-RNA complexes. By applying this tool to human proteome, we reveal statistically significant matching between the composition of mRNA sequences and base-binding preferences of protein sequences they code for. For example, purine density profiles of mRNA sequences mirror guanine affinity profiles of cognate protein sequences with quantitative accuracy (median Pearson correlation coefficient R = -0.80 across the entire human proteome). Notably, statistically significant anti-matching is seen only in the case of adenine. Our results provide strong evidence for the stereo-chemical foundation of the genetic code an...Continue Reading

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Citations

Nov 21, 2013·Nature Communications·Anton A PolyanskyBojan Zagrovic
Jul 30, 2015·Physical Chemistry Chemical Physics : PCCP·Matea HajnicBojan Zagrovic
Feb 28, 2014·RNA Biology·Bojan Zagrovic
Mar 11, 2015·Nucleic Acids Research·Mario Hlevnjak, Bojan Zagrovic
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
May 24, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Jacques Demongeot, Hervé Seligmann
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
Nov 5, 2020·Quarterly Reviews of Biophysics·Horst H KlumpKenneth J Breslauer
Dec 8, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Alexandros ArmaosGian Gaetano Tartaglia
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Oct 9, 2020·Gene·Jacques Demongeot, Hervé Seligmann
Feb 3, 2021·Open Biology·K A Dill, L Agozzino
May 28, 2021·Molecular Biology and Evolution·Haiqing Xu, Jianzhi Zhang
Aug 3, 2017·Journal of Chemical Theory and Computation·Anita de RuiterBojan Zagrovic

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Methods Mentioned

BETA
X-ray
nuclear magnetic resonance

Software Mentioned

DAVID EASE
PyMol
DAVID functional annotation server
MATLAB
IUpred

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