ストレス下でリボソームが対を形成する生存戦略を解明(Ribosomes in Pairs: a survival strategy inside stressed cells)

2026-02-19 マックス・プランク研究所

<関連情報>

• https://www.mpg.de/26161216/ribosomes-in-pairs-a-survival-strategy-inside-stressed-cells
• https://www.science.org/doi/10.1126/science.adr4287

リボソームRNA伸長セグメントは、不活性な動物リボソームのオリゴマー形成を媒介する Ribosomal RNA expansion segments mediate the oligomerization of inactive animal ribosomes

Andre Schwarz, Mara Mueller, Helene Will, Lea Dietrich, […] , and Erin M. Schuman
Science  Published:19 Feb 2026

Editor’s summary

Ribosomes are the molecular machines that make proteins within all cells. When stressed, cells reduce their synthesis of new proteins to conserve energy and mount a survival response. Schwarz et al. found that during stress, inactive mammalian ribosomes sequester together in pairs called “disomes.” The linkage between the two ribosomes is mediated by so-called expansion segments, which are poorly understood insertions in ribosomal RNA molecules. A comparative sequence analysis indicated that expansion segment function could be widespread across animal species. Thus, a ribosomal RNA-driven mechanism drives the reorganization of ribosomes during the stress response of animal cells. —Stella M. Hurtley

Structured Abstract

INTRODUCTION

Ribosomes, the molecular machinery that translates mRNA into proteins, are composed of ribosomal RNA (rRNA) and proteins. rRNA is highly conserved from bacteria to humans and drives the essential reactions for protein synthesis. Adjacent to the highly conserved core of rRNA, there are large insertions in the rRNA of complex organisms that are referred to as expansion segments (ESs). The functions of ESs remain mostly enigmatic.

RATIONALE

Despite the fundamental importance of ribosomes for cellular function within the cell, it is not well understood how animal cells optimally adapt their ribosome populations to changing environmental conditions. For example, when exposed to a stressor, how do animal cells conserve their ribosome population to quickly mount a recovery response when that stressor is finally removed? In bacteria, it is known that in response to environmental stressors, inactive ribosomes are sequestered into so-called hibernating dimers, pairs of inactive ribosomes. Although there exist observations of ribosome-ribosome interactions in animal cells dating back to the 1960s, it has remained an open question whether animal cells employ a similar mechanism.

RESULTS

In this study, we examined how ribosomes—the protein synthesis machinery—respond to stress in animal cells. We observed that stress led to the formation of ribosome-ribosome dimers (disomes) in rodent brain cells. Cryo–electron tomography revealed that the stress-induced ribosome dimers were indeed inactive (hibernating) and physically touching one another. When we zoomed in on the ribosome-ribosome linkage point, we observed that the interaction was mediated by an ES present in each rRNA molecule that homodimerizes with itself. We found that the self-dimerization of this ES, where complementary nucleotides interact in a “kissing loop,” was necessary and sufficient to confer disome formation, resulting in a proliferative advantage to dividing cells and increased resistance to long-term stress. Whether or not a species has this precise ES sequence, which is variable across the animal kingdom, predicts whether cells from that animal can form stress-induced dimers. Revisiting the chicken ribosome assemblies (“ribosome sheets”) observed in the 1960s, we found that these ribosome arrangements are driven by the same mechanism: interacting ESs present in the rRNA.

CONCLUSION

We discovered a previously unknown function for ESs: They enable the physical coupling of inactive ribosomes that occurs in response to stress. Animal cells use hairpin–kissing loop interactions between ESs to oligomerize inactive ribosomes. Our data show that this hibernation mechanism, present in animals ranging from rodents and chickens to primates, including humans, confers an advantage to cells.

Expansion segments drive the oligomerization of ribosomes.
The expansion segment ES31Lb does not interact in ribosomes that are engaged in active translation (A). During stress, inactive ribosomes are recruited into ES31Lb-mediated dimers. The sequence of this ES predicts dimerization across species [(B); darker shades mark species where ES31Lb is predicted to interact]. The same mechanism drives tetrasome formation in chicken during cold shock (C).Figure: M. Mueller; Electron microscopy images: A. Schwarz

Abstract

Cells down-regulate protein synthesis when stressed to conserve energy and shift resources toward repair. We found that in some mammalian cells, including neurons, stress also resulted in the formation of inactive ribosome-ribosome clusters (disomes). We used cryo–electron tomography (cryo-ET) to visualize ribosomes in situ and observed that this ribosome dimerization was mediated by a homotypic interaction of the ribosomal RNA (rRNA) expansion segment ES31Lb. ES31Lb interactions were both necessary and sufficient for disome formation and conferred a growth advantage and stress resistance to brain cells. ES31Lb is predicted to homodimerize in ~20% of chordates, including variants in both chicken and human. Cryo-ET analysis of chicken tetrasomes revealed an interaction between ES31Lb and ES9La. Thus, in animal cells, translation regulation can use a flexible component of the protein synthesis machinery—rRNA expansion segments.