A new family of ribosome hibernation factors in Archaea

madru, C.; Bourgeois, G.; Dulermo, R.; Figuigui, K.; Duboc, C.; L'haridon, S.; McTeer, L.; Kwapisz, M.; Mechulam, Y.; Clouet-d'Orval, B.; Bouvier, M.; Capeyrou, R.; Borrel, G.; Schmitt, E.; Flament, D.

doi:10.1101/2025.10.11.676729

bioRxiv · 10.1101/2025.10.11.676729

A new family of ribosome hibernation factors in Archaea

madru, C.·Bourgeois, G.·Dulermo, R.·Figuigui, K.·Duboc, C.·L'haridon, S.·McTeer, L.·Kwapisz, M.·Mechulam, Y.·Clouet-d'Orval, B.·Bouvier, M.·Capeyrou, R.·Borrel, G.·Schmitt, E.·Flament, D.

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Abstract

Ribosome hibernation preserves translation machinery during stress, yet its mechanisms in Archaea remain poorly defined. Here we identify Hib, a previously unrecognized family of hibernation factors widespread in Archaea. Deletion of hib in Thermococcus barophilus delays recovery from stationary phase and reduces 70S ribosome pools, establishing its role in ribosome preservation. Hib displays a unique modular architecture, combining a bacterial-like HPF/RaiA domain with a Cystathionine Beta Synthase module. High-resolution cryo-EM structures of reconstituted and in cell-extracted Hib:ribosome complexes from Pyrococcus abyssi identify three conformations encompassing the positions of tRNAs at A, P and E sites during translation. Thus, Hib acts as a hibernation factor blocking all states of the dynamic translation process, preserving the ribosome from dissociation and degradation. Our findings define Hib as a key hibernation factor in Archaea and provide a framework for understanding ribosome dormancy and adaptation across all domains of life. Beyond the discovery of Hib, a comprehensive phylogenetic analysis highlights the evolutionary relationships between prevalent ribosome hibernation factors across Bacteria and Archaea.

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madru, C., Bourgeois, G., Dulermo, R., Figuigui, K., Duboc, C., L'haridon, S., McTeer, L., Kwapisz, M., Mechulam, Y., Clouet-d'Orval, B., Bouvier, M., Capeyrou, R., Borrel, G., Schmitt, E., Flament, D.. 2025-10-11. A new family of ribosome hibernation factors in Archaea. https://doi.org/10.1101/2025.10.11.676729

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