Binding Site Occupancy with Competition Interactions in Equilibrium

Abstract

Based on the widespread and rather unspecific binding of HuR, this section presents a simple, but quantitative equilibrium model of RBPs interacting with a complex, and large pool of RNA. Many RBPs (such as HuR) are described to be not themselves catalytically active with respect to the bound RNA, but to “recruit” (e.g., by protein–protein interactions) other factors, or to prevent such factors from binding. The efficacy of such indirect function therefore depends on site occupancy. Investigating the consequences of a large pool of RNA sequence on site occupancies can contribute to our basic understanding of post-transcriptional regulation, and help to understand the effects of RBP perturbation experiments such as RNAi knock downs or over-expression. Indeed, we find that binding site competition renders site occupancies robust and linear and introduces the possibility of “crosstalk” between transcripts, especially when a large number of strong binding sites contained in a highly expressed “sponge” transcript are considered.