Structure of the human mitochondrial RNA degradosomereveals a distinct mode of helicase-nuclease coupling
- 1University Medical Center Goettingen
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.
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BibTeX
@misc{prado2026structure,
title = {{Structure of the human mitochondrial RNA degradosomereveals a distinct mode of helicase-nuclease coupling}},
author = {P. F. V. do Prado and S. Sharma and A. Bhatta and A. Vuckovic and M. P. Marani and A. P. L. David and B. Kuhle and H. S. Hillen},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.06.749684},
url = {https://www.biorxiv.org/content/10.64898/2026.09.06.749684v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Structure of the human mitochondrial RNA degradosomereveals a distinct mode of helicase-nuclease coupling
AU - P. F. V. do Prado
AU - S. Sharma
AU - A. Bhatta
AU - A. Vuckovic
AU - M. P. Marani
AU - A. P. L. David
AU - B. Kuhle
AU - H. S. Hillen
PY - 2026
DA - 2026/09/06
PB - bioRxiv
DO - 10.64898/2026.09.06.749684
UR - https://www.biorxiv.org/content/10.64898/2026.09.06.749684v1
AB - 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.
ER -