Human mitochondrial helicase Twinkle has RNA binding, annealing, and strand-exchange activities.

ABSTRACT: Twinkle is the sole replicative helicase in human mitochondria, essential for mitochondrial DNA replication. Beyond its canonical unwinding activity, Twinkle has non-canonical activities, including DNA annealing and strand-exchange. Here, we show that these non-canonical activities extend to RNA. Twinkle binds RNA and catalyzes RNA:DNA hybrid formation through annealing, strand-exchange, and toehold-mediated strand displacement. Twinkle can unwind RNA:DNA forks when loaded onto the DNA tail but not the RNA tail. Although the physiological role of these RNA-related activities remains unclear, we show that Twinkle can strand-exchange an RNA downstream of a stalled replication fork to restart replication. The annealing/strand-exchange activity can be involved in DNA replication initiation and

SUBMITTER: Singh A 

PROVIDER: S-EPMC12820530 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature