Effect of Single Nucleotide Polymorphisms on the structure of long noncoding RNAs and their interaction with RNA Binding Proteins

Abstract

Long non-coding RNAs (lncRNA) are emerging as a new class of regulatory RNAs with remarkable potential to be utilized as therapeutic targets against many human diseases. Several genome-wide association studies (GWAS) have catalogued Single Nucleotide Polymorphisms (SNPs) present in the noncoding regions of the genome, transcribing lncRNAs. In this study, we have selected 67 lncRNAs with GWAS-tagged SNPs and have also investigated their role in affecting the local secondary structures. The majority of the SNPs lead to changes in the secondary structure of lncRNA to a different extent by altering the base pairing patterns. These structural changes in lncRNA are also manifested in form of alteration in the binding site for RNA binding proteins (RBPs) along with affecting their binding efficacies. Ultimately, these structural modifications may influence the transcriptional and post-transcriptional pathways of these RNAs, leading to the causation of diseases. Hence, it is important to understand the possible underlying mechanism of RBPs in association with GWAS-tagged SNPs in human diseases.