Summary: Neurons are high-energy cells that must find ways to survive when nutrients are scarce. New research has discovered a fascinating survival mechanism: neurons pair up their protein factories (ribosomes) into inactive “disomes” to save energy.
Unlike bacteria, which use proteins to link ribosomes, animal cells use long, flexible RNA “tentacles” called expansion segments. These segments form a “kissing loop” that locks ribosomes together during stress, protecting these expensive molecular machines until favorable conditions return.
Key Facts
- The Energy-Saving Disome: When stressed (by cold or lack of food), animal cells assemble inactive ribosomes into pairs called disomes to halt costly protein production.
- RNA Tentacles: The connection is made by a specific ribosomal RNA segment called “31b,” an expansion segment that acts like a tentacle protruding from the ribosome.
- The “Kissing Loop”: These RNA tentacles bind to each other through complementary sequences, forming a precise, reversible lock.
- Cryo-ET Visualization: Researchers used cryogenic electron tomography to see these ribosome pairs directly inside intact, frozen cells for the first time.
- Evolutionary Clue: Expansion segments have grown larger over the course of evolution; this study reveals they play a key role in how complex organisms manage cellular stress.
Source: Max Planck Society
Ribosomes are large molecular machines made of protein and RNA that build all proteins in the cell.
Because protein production is extremely energy-intensive, cells rapidly reduce protein synthesis when stressed. It has long been known that bacterial cells pair their inactive ribosomes into so-called “hibernating disomes” however, such structures had not previously been identified in animal cells.
An unexpected role for ribosomal RNA during cellular stress
Using advanced imaging techniques, Erin Schuman and her team at the Department of Synaptic Plasticity at the Max Planck Institute for Brain Research in Frankfurt discovered that stressed animal cells – including neurons – assemble inactive ribosomes into tightly linked pairs, known as disomes. These ribosome pairs are not accidental collisions or artifacts, but a regulated and reversible response to stress.
The new study was published today in Science.
“Surprisingly, the two ribosomes are not held together by proteins, as is common in bacteria. Instead, the connection is made by a specific piece of ribosomal RNA called an expansion segment”, explains one of the lead authors, postdoctoral researcher, Andre Schwarz.
Expansion segments are long, flexible RNA “tentacles” that protrude from ribosomes and have grown larger over the course of evolution. Although they are a prominent feature of animal ribosomes, their functions only just started to emerge. This study now shows that one particular expansion segment, called “31b”, is both necessary and sufficient to link ribosomes together during stress
. At the molecular level, the expansion segment forms a precise RNA-RNA interaction – a so-called “kissing loop” – in which identical RNA loops bind each other through complementary sequences. Disrupting this interaction prevents disome formation, stunts cellular growth and makes cells more sensitive to stress.
Seeing ribosomes inside cells
A key strength of the study was the ability to visualize ribosomes directly inside intact cells using cryogenic electron tomography (Cryo-ET). Cryo-ET is a powerful 3D imaging technique that uses an electron microscope to see inside frozen biological samples (cells, organelles, molecules) with very high resolution. This approach allowed the team to visualize ribosomes in their native environment and resolve how they re-organize during stress.
The study combined an unusually broad range of techniques, including cell biology, biochemistry, yeast and mammalian cell genetic engineering, and high-resolution structural imaging.
“One major challenge was manipulating ribosomal RNA, which is encoded by hundreds to thousands of nearly identical gene copies in animal genomes. We overcame this hurdle by engineering hybrid ribosomes in yeast and by introducing small RNA molecules that specifically disrupted ribosome pairing in animal cells”, says Mara Mueller, graduate student in the Schuman Lab and co-first author of the study.
A new view of translation control
„Our findings uncover a previously unknown mechanism by which animal cells regulate protein synthesis during stress – one that relies on RNA structure. The study reveals a new function for ribosomal RNA expansion segments which have been rather mysterious”, says Erin Schuman.
By temporarily storing ribosomes in inactive pairs, cells protect these costly machines and enable rapid recovery once favorable conditions return. The discovery opens new avenues for understanding how cells adapt to stress and how ribosome organization contributes to health and disease.
Key Questions Answered:
A: Making proteins is the most energy-intensive thing a cell does. In a crisis (like starvation), a cell has to cut its “spending.” By pairing up ribosomes and putting them in “hibernation,” the cell saves massive amounts of energy to stay alive.
A: The study found that if the RNA “kissing loop” is disrupted, cells cannot properly enter hibernation mode. This stunts growth and makes the cells much more likely to die when conditions get tough.
A: They used Cryo-ET, which involves “plunge-freezing” cells so quickly that the water doesn’t form ice crystals. This preserves the cell in its natural state, allowing an electron microscope to take high-resolution 3D pictures of the molecules inside.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this genetics and neuroscience research news
Author: Irina Epstein
Source: Max Planck Institute
Contact: Irina Epstein – Max Planck Institute
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“rRNA expansion segments mediate the oligomerization of inactive animal ribosomes” by Andre Schwarz, Mara Mueller, Helene Will, Lea Dietrich, Stefano L. Giandomenico, Georgi Tushev, Ina Bartnik, Iskander Khusainov, Claudia M. Fusco, Erin M. Schuman. Science
DOI:10.1126/science.adr4287
Abstract
rRNA expansion segments mediate the oligomerization of inactive animal ribosomes
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.
