Stressed Cells Assemble Ribosomes into Pairs

Stressed animal cells assemble inactive ribosomes into pairs using a ribosomal RNA link to conserve energy in survival mode. The Schuman Lab at the Max Planck Institute for Brain Research in Frankfurt uncovered this mechanism, revealing a new role for ribosomal RNA in stress responses, as published in Science.

Ribosomes function as the cell’s protein-making factories, using large amounts of energy to build vital proteins. During stress—such as nutrient scarcity or sudden temperature drops—cells halt protein synthesis rapidly. Bacteria have long formed “hibernating disomes” from inactive ribosome pairs, but this was previously unknown in animal cells.

Cryogenic electron tomography (Cryo-ET) revealed these disomes in stressed animal cells, including neurons. The pairs represent a regulated, reversible stress response, not mere accidents. “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 lead author Andre Schwarz.

Expansion segments are long, flexible RNA “tentacles” that have expanded evolutionarily on animal ribosomes, with emerging functions. The study identifies the “31b” expansion segment as both necessary and sufficient for pairing. It forms a “kissing loop” through complementary RNA sequences binding identical loops. Disrupting this prevents disome formation, impairs cellular growth, and increases stress vulnerability.

“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,” added Mara Mueller, co-first author.

“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,” stated Schuman.