Activation of human RNA lariat debranching enzyme Dbr1 by binding protein TTDN1 occurs though an intrinsically disordered C-terminal domain

ABSTRACT: In eukaryotic cells, the introns are excised from pre-mRNA by the spliceosome. These introns typically have a lariat configuration due to the 2′-5′ phosphodiester bond between an internal branched residue and the 5′ terminus of the RNA. The only enzyme known to selectively hydrolyze the 2′-5′ linkage of these lariats is the RNA lariat debranching enzyme Dbr1. In humans, Dbr1 is involved in processes such as class-switch recombination of immunoglobulin genes, and its dysfunction is implicated in viral encephalitis, HIV, ALS, and cancer. However, mechanistic details of precisely how Dbr1 affects these processes are missing. Here we show that human Dbr1 contains a disordered C-terminal domain through sequence analysis and nuclear magnetic resonance. This domain stabilizes Dbr1 in vitro by red

SUBMITTER: Clark N 

PROVIDER: S-EPMC10470207 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature