Novel L-RNA Aptamer Controls APP Gene Expression in Cells by Targeting RNA G-Quadruplex Structure

• DOI: 10.1021/acsami.2c06390
• Publication Date: 2022-06-28T14:18:30Z
• Authors: Haizhou Zhao; Hei Yuen Wong; Danyang Ji; Kaixin Lyu; Chun Kit Kwok
• Keywords: Aptamer; G-quadruplex; Nucleic acid structure; Riboswitch; RNA recognition motif

Guanine quadruplex (G4) structure is a four-stranded nucleic acid secondary motif with unique chemical properties and important biological roles. Amyloid precursor protein (APP) an Alzheimer's disease (AD)-related gene, recently, we reported the formation of RNA G4 (rG4) at 3'UTR APP mRNA demonstrated its repressive role in translation. Herein, apply rG4-SELEX to develop novel L-RNA aptamer, L-Apt.8f, which binds D-rG4 strongly subnanomolar affinity. We structurally characterize aptamer find that it contains thermostable parallel motif, mutagenesis analysis identifies key nucleotides are involved target recognition. also reveal L-Apt.8f-APP interaction enantiomeric-, magnesium ion-, potassium ion-dependent. Notably, L-Apt.8f preferentially recognizes rG4 over other structural motifs, can control reporter gene native transcript translation cells. Our work introduces strategy reports new L-aptamer candidate structure, laid foundation for further applying as class biomolecule practical L-aptamer-based targeting controlling expression