Structural basis for water modulating RNA duplex formation in the CUG repeats of myotonic dystrophy type 1.

ABSTRACT: Secondary structures formed by expanded CUG RNA are involved in the pathobiology of myotonic dystrophy type 1. Understanding the molecular basis of toxic RNA structures can provide insights into the mechanism of disease pathogenesis and accelerate the drug discovery process. Here, we report the crystal structure of CUG repeat RNA containing three U-U mismatches between C-G and G-C base pairs. The CUG RNA crystallizes as an A-form duplex, with the first and third U-U mismatches adopting a water-mediated asymmetric mirror isoform geometry. We found for the first time that a symmetric, water-bridged U-H₂O-U mismatch is well tolerated within the CUG RNA duplex, which was previously suspected but not observed. The new water-bridged U-U mismatch resulted in high base-pair opening and

SUBMITTER: Wang SC 

PROVIDER: S-EPMC10316006 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature