Crystal structure of dimeric human PNPase reveals why disease-linked mutants suffer from low RNA import and degradation activities.

ABSTRACT: Human polynucleotide phosphorylase (PNPase) is an evolutionarily conserved 3'-to-5' exoribonuclease principally located in mitochondria where it is responsible for RNA turnover and import. Mutations in PNPase impair structured RNA transport into mitochondria, resulting in mitochondrial dysfunction and disease. PNPase is a trimeric protein with a doughnut-shaped structure hosting a central channel for single-stranded RNA binding and degradation. Here, we show that the disease-linked human PNPase mutants, Q387R and E475G, form dimers, not trimers, and have significantly lower RNA binding and degradation activities compared to wild-type trimeric PNPase. Moreover, S1 domain-truncated PNPase binds single-stranded RNA but not the stem-loop signature motif of imported structured RNA, suggesting t

SUBMITTER: Golzarroshan B 

PROVIDER: S-EPMC6144817 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature