Poster abstracts
Poster number 145 submitted by Michael Widom
mRNA-mediated cooperativity between microRNA target sites
Natalie Hanisch (Department of Mathematics, University of Nebraska, Kearney), Michael Widom (Department of Physics, Carnegie Mellon University)
Abstract:
MicroRNAs downregulate expression of targeted genes. Experimental and bioinformatic evidence suggests multiple target sites on a common gene can cooperatively enhance downregulation[1,2], but the precise mechanism of cooperation is not known. Recent theoretical studies suggest target site interactions can be mediated through the RNA sequence of the gene itself[3]. We confirm the presence of both positive and negative cooperativity for mammalian microRNA targets, with a distance-dependent weighting towards positive cooperativity (enhanced binding affinity). We show that positivity of cooperativity is greater for well-conserved target sites than for poorly conserved ones.
References:
[1] A. Grimson, et al., "MicroRNA targeting specificity in mammals: determinants beyond seed pairing", Mol. Cell 27 (2007) 91-105
[2] P. Saetrom, et al., "Distance constraints between microRNA target sites dictate efficacy and cooperativity", Nucl. Acids Res. 35 (2007) 2333-42
[3] Y.-H. Lin and R. Bundschuh, "Interplay between single-stranded binding proteins on RNA secondary structure", Phys. Rev. B 88 (2013) 052707
Keywords: microRNA, cooperativity