Can Antisense lncRNA bind to the product of its sense pair?

Abstract

Long non-coding RNAs (lncRNAs) account for a major proportion of the transcriptional output in complex organismal genomes. Their emergence as auxiliary regulators of gene expression as well as their roles in metastasis and cancer progression has put them in the limelight. LncRNAs perform multitudes of functions and often moonlight as regulators, scaffolds and guides. Most lncRNAs are cell and tissue specific and can act as markers for diseases as well as targets for therapeutic interventions. LncRNAs are also known to make use of higher order structures such as G-quadruplexes (G4) to facilitate complex functions and interactions. THAP9-antisense1 (AS1) is a lncRNA coding gene (recently annotated by Ensembl) that codes for 12 lncRNA transcripts and has been implicated in many disease pathologies like gastric cancer, spontaneous neutrophil apoptosis, hepatocellular carcinoma, and the progression of oesophageal cancer. It is the antisense gene pair of the THAP9 gene ( a transposase derived gene) with which it shares a promoter. THAP9-AS1 has been reported to be dysregulated during stress and several cancers. However, the exact role of the lncRNA is not well understood. Bioinformatics driven strategies are used to identify putative quadruplex forming sequences (PQSs) within the lncRNA THAP9-AS1. The identified PQSs are further validated using biophysical, spectroscopic and molecular biology driven techniques. The importance of each G-tract in the formation of a particular RNA G-quadruplex (rG4) is studied via the investigation of several deletion mutants. The findings demonstrate the rG4 forming potential of the identified PQSs within THAP9-AS1.