Structural toggle in the RNaseH domain of Prp8 helps balance splicing fidelity and catalytic efficiency.

ABSTRACT: Pre-mRNA splicing is an essential step of eukaryotic gene expression that requires both high efficiency and high fidelity. Prp8 has long been considered the "master regulator" of the spliceosome, the molecular machine that executes pre-mRNA splicing. Cross-linking and structural studies place the RNaseH domain (RH) of Prp8 near the spliceosome's catalytic core and demonstrate that prp8 alleles that map to a 17-aa extension in RH stabilize it in one of two mutually exclusive structures, the biological relevance of which are unknown. We performed an extensive characterization of prp8 alleles that map to this extension and, using in vitro and in vivo reporter assays, show they fall into two functional classes associated with the two structures: those that promote error-prone/eff

SUBMITTER: Mayerle M 

PROVIDER: S-EPMC5422793 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature