Biochemical and structural basis of Dicer helicase function unveiled by resurrecting ancient proteins.

ABSTRACT: A fully functional Dicer helicase, present in the modern arthropod, uses energy generated during ATP hydrolysis to power translocation on bound dsRNA, enabling the processive dsRNA cleavage required for efficient antiviral defense. However, modern Dicer orthologs exhibit divergent helicase functions that affect their ability to contribute to antiviral defense, and moreover, mechanisms that couple ATP hydrolysis to Dicer helicase movement on dsRNA remain enigmatic. Here, we used biochemical and structural analyses of ancestrally reconstructed Dicer helicases to map evolution of dsRNA binding affinity, ATP hydrolysis and translocation. We found that loss of affinity for dsRNA occurred early in Dicer evolution, coinciding with a decline in translocation activity, despite preservation of ATP h

SUBMITTER: Aderounmu AM 

PROVIDER: S-EPMC11844470 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature