RNA G-quadruplex structure-based PROTACs for targeted DHX36 protein degradation and gene activity modulation in mammalian cells.

ABSTRACT: RNA G-quadruplexes (rG4s) are non-canonical secondary nucleic acid structures found in the transcriptome. They play crucial roles in gene regulation by interacting with G4-binding proteins (G4BPs) in cells. rG4-G4BP complexes have been associated with human diseases, making them important targets for drug development. Generating innovative tools to disrupt rG4-G4BP interactions will provide a unique opportunity to explore new biological mechanisms and potentially treat related diseases. Here, we have rationally designed and developed a series of rG4-based proteolytic targeting chimeras (rG4-PROTACs) aimed at degrading G4BPs, such as DHX36, a specific G4BP that regulates gene expression by binding to and unraveling rG4 structures in messenger RNAs (mRNAs). Our comprehensive data and systema

SUBMITTER: Zhang K 

PROVIDER: S-EPMC11780864 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature