Structure of the human mitochondrial RNA degradosome reveals a distinct mode of helicase–nuclease coupling
TL;DR
The cryo-EM structure of the complete human mitochondrial RNA degradosome bound to RNA is reported and reveals an asymmetric heteropentamer composed of a SUV3 dimer and the trimeric PNPase, revealing a mode of helicase–nuclease coupling distinct from other RNA degradation machineries.
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.