Poster abstracts
Poster number 78 submitted by Yi-Hsuan Lin
Structure-mediated cooperativity between single-stranded RNA binding partners on 5' and 3'UTRs
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 and C. elegans mRNA sequences, and find that structure-mediated cooperativity is a generic feature of mRNA sequences. By comparing the measurements of human and C. elegans mRNAs, we find that the strength of the cooperativity is strongly related to the lengths of UTRs. Moreover, we generate a group of RNA sequences by replacing the coding regions of human mRNAs with a fixed coding region sequence, and discover that the cooperativities of these RNAs have statistical properties very similar to the original human mRNAs. We thus conclude that cooperativity between two proteins bound on the 5' and the 3' UTR, respectively, can be mediated by the secondary structures of the two UTR sequences independently of the intervening coding sequences. We also apply an evolutionary algorithm to several human RNA sequences, and discover that artificially evolved sequences can support extremely strong cooperativities.
Keywords: RNA-protein interactions, cooperativity, RNA structure