Long-form hibernation-promoting factor coordinates 100S assembly and translational repression
- 1Shandong University
Abstract
Ribosome hibernation mediated by long-form hibernation-promoting factor (HPF) requires coordination of ribosome dimerization and translational repression, but how these functions are integrated remains unclear. Here, we present cryo-EM structures of native 100S from a deep-sea Bacillus isolate, revealing a conformationally heterogeneous 100S population. Beyond the established roles of the HPF N-terminal domain (NTD) in decoding-center occlusion and the C-terminal domain (CTD) in dimerization, our analyses reveal additional contributions from the Linker and a charged CTD surface near the 16S rRNA 3' terminus containing the anti-Shine-Dalgarno (aSD) sequence. Linker substitutions differentially affect translational repression while retaining 100S formation, with distinct effects of the two Linker segments. Mutation of the charged CTD surface enhances translational repression while retaining robust 100S formation, suggesting an additional role beyond CTD-mediated ribosome dimerization. Functional analyses in an E. coli cell-free translation system further show that the inhibitory activity of individual HPF regions varies with translational context. Together, these findings support a modular model in which the NTD, Linker, and CTD make distinct but interconnected contributions to 100S assembly and translational repression.
Related
- Temozolomide Induces Aberrant RNA Alkylation and Widespread Translational Repression
- The carbohydrate utilization regulator Cbr1 coordinates nutrient-specific gene activation with selective carbon catabolite repression in a basidiomycete yeast
- MacroH2A-mediated gene repression through nucleosome compaction and remodeling inhibition
- A Hox-dependent anchoring mechanism mediates transcriptional repression of autophagy-related genes at the nuclear periphery
- ATRA resistance conferred by a clustered subset of hotspot PML::RARA mutations enhancing basal repression rather than precluding transactivation
BibTeX
@misc{li2026longform,
title = {{Long-form hibernation-promoting factor coordinates 100S assembly and translational repression}},
author = {W. Li and M. Wu and Y. Bai and C. Zhang and C. Yi and R. Zheng and L. Qi and L. Zhu and Z. Zhang and C. Sun},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.02.756224},
url = {https://www.biorxiv.org/content/10.64898/2026.10.02.756224v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Long-form hibernation-promoting factor coordinates 100S assembly and translational repression
AU - W. Li
AU - M. Wu
AU - Y. Bai
AU - C. Zhang
AU - C. Yi
AU - R. Zheng
AU - L. Qi
AU - L. Zhu
AU - Z. Zhang
AU - C. Sun
PY - 2026
DA - 2026/10/02
PB - bioRxiv
DO - 10.64898/2026.10.02.756224
UR - https://www.biorxiv.org/content/10.64898/2026.10.02.756224v1
AB - Ribosome hibernation mediated by long-form hibernation-promoting factor (HPF) requires coordination of ribosome dimerization and translational repression, but how these functions are integrated remains unclear. Here, we present cryo-EM structures of native 100S from a deep-sea Bacillus isolate, revealing a conformationally heterogeneous 100S population. Beyond the established roles of the HPF N-terminal domain (NTD) in decoding-center occlusion and the C-terminal domain (CTD) in dimerization, our analyses reveal additional contributions from the Linker and a charged CTD surface near the 16S rRNA 3' terminus containing the anti-Shine-Dalgarno (aSD) sequence. Linker substitutions differentially affect translational repression while retaining 100S formation, with distinct effects of the two Linker segments. Mutation of the charged CTD surface enhances translational repression while retaining robust 100S formation, suggesting an additional role beyond CTD-mediated ribosome dimerization. Functional analyses in an E. coli cell-free translation system further show that the inhibitory activity of individual HPF regions varies with translational context. Together, these findings support a modular model in which the NTD, Linker, and CTD make distinct but interconnected contributions to 100S assembly and translational repression.
ER -