Cognate RNA-Binding Modes by the Alternative-Splicing Regulator MBNL1 Inferred from Molecular Dynamics.

ABSTRACT: The muscleblind-like protein family (MBNL) plays a prominent role in the regulation of alternative splicing. Consequently, the loss of MBNL function resulting from sequestration by RNA hairpins triggers the development of a neuromuscular disease called myotonic dystrophy (DM). Despite the sequence and structural similarities between the four zinc-finger domains that form MBNL1, recent studies have revealed that the four binding domains have differentiated splicing activity. The dynamic behaviors of MBNL1 ZnFs were simulated using conventional molecular dynamics (cMD) and steered molecular dynamics (sMD) simulations of a structural model of MBNL1 protein to provide insights into the binding selectivity of the four zinc-finger (ZnF) domains toward the GpC steps in YGCY RNA sequence. In accor

SUBMITTER: Gonzalez AL 

PROVIDER: S-EPMC9780971 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature