Single nucleotide polymorphisms affect RNA-protein interactions at a distance through modulation of RNA secondary structures

RNA-protein interactions play an important role in regulating gene expression. Since RNA-protein interactions are affected by RNA secondary structure, single nucleotide polymorphisms in the vicinity of protein binding sites can affect these interactions. This provides a mechanism for single nucleotide polymorphisms outside coding regions and outside the actual protein binding sites to convey a phenotype. Here, we use a modified version of the Vienna RNA folding package and PAR-CLIP data for HuR (ELAVL1) in humans to characterize the genome-wide effect of single nucleotide polymorphisms on HuR binding and show that they can have a many-fold effect on the affinity of HuR binding to RNA transcripts from tens of bases away. We also find that the effect of single nucleotide polymorphisms on protein binding appears to be under selection, with the minor alleles tending to make it harder for a protein to bind.