title: Evidence of direct complementary interactions between messenger RNAs and their cognate proteins.
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 and suggest that mRNAs and cognate proteins may in general be directly complementary to each other and associate, especially if unstructured.
authors.affiliation: Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Polyansky
authors.forename: Bojan
authors.initials: B
authors.lastname: Zagrovic
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001482:Base Composition; D003062:Codon; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011687:Purines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020539:Sequence Analysis, Protein; D017423:Sequence Analysis, RNA
chemical_list: D000596:Amino Acids; D003062:Codon; D011687:Purines; D011743:Pyrimidines; D012333:RNA, Messenger; D016601:RNA-Binding Proteins