LAUSR

Nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are macromolecules that are essential for all known forms of life. Besides storing genetic information, nucleic acids regulate key biological processes inside the cell, including genes expression, DNA replication, recombination and repair. They are also involved in diseases such as cancer and neurological disorders therefore represent potential drug targets. The DNA and RNA execute their regulatory functions by adopting diverse secondary and tertiary conformations which are essential for specific molecular recognition of their cognate targets. Nucleic acids adopt diverse conformations through several types of hydrogen bonding patterns. The canonical double-stranded structure consists of two antiparallel strands intertwined by Watson-Crick A-T and G-C base pairs. On the other hand, the non-canonical structures include G-quadruplexes, i-motifs, triplexes and cruciform hairpins, etc. are formed by alternative base pairings such as Hoogsteen and Wobble base pairs. Given their crucial biological functions, non-canonical structures are of great interests in genetics, molecular biology and drug discovery. The ability of nucleic acids to adopt different conformations depends on the sequence. The abnormal expansion of certain nucleic acid sequences has been linked to numerous neurological diseases. For example, a hexanucleotide repeat expansion mutation in chromosome 9 open reading frame 72 (C9orf72) gene causes neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), through the formation of non-canonical nucleic acid structures in the genome. Recent technological advances have uncovered the additional functional roles of non-canonical nucleic acids in the pathobiology of the diseases. Using high-throughput genomic, structural and computational methods, non-canonical nucleic acid structures have emerged as promising tools for various applications such as DNA nanotechnology, gene therapy and drug discovery. OPEN ACCESS