The relationship between mRNAs and the proteins they encode is one of the key defining characteristics of life at the molecular level. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: This work was supported by the European Research Council to BZ (Starting Independent grant PROTINT 279408). Received: MaAccepted: JPublished: July 27, 2017Ĭopyright: © 2017 Bartonek, Zagrovic. Dokholyan, University of North Carolina at Chapel Hill, UNITED STATES PLoS Comput Biol 13(7):Įditor: Nikolay V. As a whole, our work provides a quantitative foundation for understanding the putative messenger RNA/protein complementarity with implications in different areas of RNA/protein biology including transcription, translation, splicing and viral assembly.Ĭitation: Bartonek L, Zagrovic B (2017) mRNA/protein sequence complementarity and its determinants: The impact of affinity scales. Specifically, we define the constraints that need to be satisfied by physical scales for the complementarity to hold and show that the previously derived nucleobase/amino-acid affinity scales indeed satisfy these constraints. Here, we explore different amino-acid scales used in the above analysis to assess which of their properties dictate the observed matching. Based on this, it has been suggested that these molecules may interact with each other specifically and in a co-aligned fashion, especially when unstructured. Specifically, density profiles of certain groups in messenger RNA sequences directly match the affinity profiles for precisely those groups in protein sequences they encode. Messenger RNAs and proteins, two essential types of biopolymers, have recently been shown to exhibit closely related, complementary physicochemical properties. Our results expose the dependence of cognate mRNA/protein sequence complementarity on the properties of the underlying nucleobase/amino-acid affinity scales and provide quantitative constraints that any physical scales need to satisfy for the complementarity to hold. Finally, we characterize suboptimal scales and show that intermediate-to-high complementarity can be reached by substantially diverse scales, but with select amino acids contributing disproportionally. This provides support for the claim that mRNA/protein sequence complementarity may indeed be related to binding between the two. 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. 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. 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. Here, we study the dependence of mRNA/protein sequence complementarity on the properties of the nucleobase/amino-acid affinity scales used. Based on this, it has been proposed that cognate mRNA/protein pairs may bind in a co-aligned manner, especially if unstructured. 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.
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