Professor Bojan Zagrovic, University of Vienna

"RNA-protein interactions and the structure of the genetic code"

About the Seminar:

The relationship between mRNA and protein sequences as embodied in the universal genetic code is a cornerstone of modern-day molecular biology. However, a potential connection between the physicochemical properties of mRNAs and their cognate proteins, with implications concerning both the code’s origin and mRNA-protein interactions in general, remains largely unexplored. As our central result, we have recently revealed a robust, statistically significant matching between the composition of mRNA coding sequences and the base-binding preferences of their cognate protein sequences. Consistent results are obtained regardless of how the latter were derived, including: 1) experimental and computational interaction propensity scales capturing the behavior of amino acids in aqueous solutions of nucleobase analogs, 2) computational absolute binding free energies between individual aminoacid sidechain analogs and nucleobases in different solvents, and 3) knowledge-based interaction preferences of amino acids for different nucleobases. As an illustration, purine density profiles of mRNA sequences mirror the knowledge-based guanine affinity profiles of their cognate protein sequences with quantitative accuracy (median Pearson correlation coefficient |R| = 0.80 across the entire human proteome). Overall, our results support as well as redefine the stereochemical hypothesis concerning the code’s origin, the idea that it evolved from direct interactions between amino acids and the appropriate bases. Moreover, our findings support the possibility of direct complementary interactions between mRNAs and their cognate proteins even in present-day cells, especially if both are unstructured, with implications extending to different facets of nucleic acid/protein biology.

References

1. Hlevnjak M, Polyansky AA & Zagrovic B, “Sequence signatures of direct complementarity between mRNAs and cognate proteins on multiple levels”, Nucleic Acids Research, 2012, 40, 8874-8882.
2. Polyansky AA & Zagrovic B, “Evidence of direct complementary interactions between messenger RNAs and their cognate proteins”, Nucleic Acids Research, 2013, 41, 8434-8443.
3. Polyansky AA, Hlevnjak M & Zagrovic B, “Proteome-wide analysis reveals clues of complementary interactions between mRNAs and their cognate proteins as the physicochemical foundation of the genetic code”, RNA Biology, 2013, 10, 1248-1254.
4. de Ruiter & Zagrovic B (2015) “Absolute binding-free energies between standard RNA/DNA nucleobases and amino-acid sidechain analogs in different environments”, Nucleic Acids Research, 43, 708–718.

About the Speaker:

Professor Bojan Zagrovic is an Associate Professor in the Department of Structural and Computational Biology at the Max F. Perutz Laboratories (MFPL) & University of Vienna. He started work at the MFPL in 2010 as a junior group leader, studied biochemical sciences at Harvard University and biophysics at Stanford University. After his postdoctoral stay at the ETH Zürich, he led the Computational Biology group at the Mediterranean Institute for Life Sciences in Split, Croatia. He has been awarded several renowned scientific awards and grants, among the most recent the Starting Independent Researcher Grant of the European Research Council and the START prize by the Austrian Science Fund (FWF).