Poster abstracts

Poster number 77 submitted by Yi-Hsuan Lin

Cooperativity between single-stranded binding proteins on RNA secondary structure

Yi-Hsuan Lin (Department of Physics, Center for RNA Biology, The Ohio State University), Ralf Bundschuh (Department of Physics, Department of Chemistry and Biochemistry, Division of Hematology, Center for RNA Biology, The Ohio State University)

Abstract:
In post-transcriptional regulation, many proteins and/or microRNAs bind to an RNA molecule to modulate its biological functions. Such process comprises multiple binding reactions, and in order to enable combinatorial gene regulation it is necessary that these binding partners of RNA communicate with each other, or in other words that their binding to the RNA exhibits cooperativity. Even in the absence of direct physical interactions between the binding partners, such cooperativity can be mediated through the secondary structure of the RNA molecule, since the secondary structure affects accessibility to the various binding sites. Here we propose a quantitative measure of this structure-mediated cooperativity that can be calculated for an arbitrary RNA sequence using computational secondary structure prediction methods. Focusing on an RNA with two binding sites, we derive a characteristic free energy difference as the measurement for describing how the binding strength of one site is affected by the occupancy of the other one. We apply this measurement to a large number of human mRNA sequences, and find that structure-mediated cooperativity is a generic feature of mRNA sequences. Most interestingly, this structure-mediated cooperativity not only affects binding sites in close proximity along the sequence but also configurations in which one binding site is located in the 5'UTR and the other binding site is located in the 3'UTR of the molecule.

Keywords: RNA-protein interactions, cooperativity, RNA structure