Structure of the human mitochondrial RNA degradosomereveals a distinct mode of helicase-nuclease coupling

Authors

do Prado, P. F. V., Sharma, S., Bhatta, A., Vuckovic, A., Marani, M. P., David, A. P. L., Kuhle, B., Hillen, H. S.

Abstract

RNA degradation shapes cellular and organellar gene expression. In human mitochondria, this process is mediated by a dedicated degradosome comprising the helicase SUV3 and the exoribonuclease PNPase, but how these enzymes assemble and cooperate to degrade structured RNA has remained unknown. Here, we report the cryo-EM structure of the complete human mitochondrial RNA degradosome bound to RNA. The structure reveals an asymmetric heteropentamer composed of a SUV3 dimer and the trimeric PNPase. Degradosome assembly is accompanied by conformational rearrangements in PNPase that reshape the RNA-entry channel and generate an asymmetric S1-domain platform for SUV3 binding. This creates a continuous electropositive path from SUV3 to PNPase, suggesting how RNA may be guided during degradation. Together, these findings reveal a mode of helicase-nuclease coupling distinct from other RNA degradation machineries and provide a structural framework for understanding human mitochondrial RNA degradation, its regulation, and association with disease.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 11 Sep 2026.

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