Discovery of a G-rich ultra stable human ncRNA G-quadruplex that binds ATP

Thermostable RNA motifs have been shown to be a unique material for building nanoparticles for many applications (Guo lab, Nature Nanotechnology, 2020 PMID: 21102465 ; 2021 PMID: 21909084 ). Here, we report the discovery of a G-rich ultra-stable human ncRNA G-quadruplex that binds ATP with a strong potential to become a drug-carrying nanoparticle. Motion is a key feature of living systems, which can be achieved with ATPase biomotors. Humans produce, metabolize, and consume ATP per day in an amount equivalent to their body weight. Due to the abundance of noncoding RNA (ncRNA) discovered in the human body, it is expected that many short or long noncoding RNAs will be involved in ATP binding and hydrolysis. This is based on the fact that, although all currently reported ATPases are proteins, only 1.5% of the human DNA genome codes for proteins, while the remaining 98.5% codes for ncRNAs that play crucial roles in regulating life functions. We discovered an endogenous human ncRNA G-quadruplex that binds ATP. This ATP-binding RNA was discovered via in vitro screening of endogenous ncRNAs extracted from human cells. This ATP-binding ncRNA, which was found to be G-quadruplex-forming, was characterized by ATP column binding and circular dichroism. The tightly folded, compact RNA nanoparticles will provide a new class of functional nanomaterials as both targets and carriers for drug conjugation and therapeutic delivery.