Jerusalem, 3 december, 2025 (TPS-IL) — Some of Earth’s hardiest microorganisms, living in volcanic craters, hot springs, and underwater vents, have evolved a remarkable ability to keep their essential cellular machinery running even in extreme heat that would destroy most life. Now, an international team led by Israel’s Weizmann Institute of Science has uncovered the chemical tricks these heat-loving microbes use in a study that may open a door to more stable vaccines, better cancer treatments, and other medical and industrial technologies.
The study, published in the peer-reviewed Cell, focused on the ribosome, a cellular structure that produces proteins in all organisms.
Ribosomal RNA undergoes chemical modifications after it is produced, but the scope and variability of these changes remained unclear. “Until recently, it was believed that RNA editing was uniform in ribosomes of different individuals and did not vary depending on the environment,” said Prof. Shraga Schwartz of the Institute’s Department of Molecular Genetics. “However, evidence has accumulated in a handful of species that editing can sometimes be dynamic and allow the ribosome structure to adapt.”
Existing methods could detect only one modification at a time. A new approach developed in Schwartz’s lab, led by Dr. Miguel A. Garcia Campos, allows 16 modifications to be examined simultaneously across dozens of RNA samples. The researchers mapped modifications in 10 single-celled species and compared them with four previously studied, deliberately selecting organisms from extreme environments.
The results were striking.
“While most bacteria and archaea have a few dozen modifications in ribosomal RNA, in hyperthermophilic species we found hundreds,” Schwartz said. “The warmer an organism’s natural environment, the more editing modifications it performs.”
The team tested whether a species could re-edit its RNA in response to temperature changes. Species accustomed to moderate conditions showed few changes, while hyperthermophiles displayed dramatic flexibility. Nearly half of their RNA modifications were dynamic, increasing as growth temperatures rose. Ribosome restructuring, they concluded, is central to survival in extreme heat.
Three types of modifications increased with temperature. One — methylation — almost always appeared alongside acetylation. “This raised the hypothesis that the modifications work together,” Schwartz said. Working with Prof. Sebastian Glatt’s group in Krakow, they tested RNA molecules with no modifications, with each separately, and with both combined. “Both methylation and acetylation stabilize RNA, but together the whole is greater than the sum of its parts,” Schwartz said.
To understand structural effects, the team partnered with Prof. Moran Shalev Ben-Ami’s group, which used cryo-electron microscopy to map ribosomes under two conditions — when the methylation enzyme was active and when silenced. Methyl groups at high temperatures formed numerous weak bonds with nearby molecules, strengthening the ribosome and reducing structural gaps.
The discovery may explain the pharmaceutical “magic methyl” — the dramatic increase in drug effectiveness sometimes seen when a methyl group is added. “It is now possible that some RNA editing changes, such as methylation and acetylation, are not isolated, and that we should decipher them as a continuous code,” Schwartz said.
The findings could help medicine and drug development. By revealing how hyperthermophiles chemically modify RNA to remain stable, scientists may design molecules that resist degradation — a major hurdle for RNA-based vaccines, cancer therapies, and gene-editing tools.
Beyond medicine, the study has industrial applications. Insights into ribosomal adaptation could allow engineers to develop microorganisms capable of efficient protein production under harsh conditions, improving biofuel generation and chemical synthesis. Discovering that RNA modifications may function as a coordinated “code” opens the door to custom-designed RNA molecules with predictable properties for diagnostics, biosensors, and therapeutics that are stable in diverse environments.
As RNA-based vaccines, diagnostics, and treatments reshape medicine, Schwartz believes these insights could drive further breakthroughs. “The natural RNA editing process has undergone billions of years of refinement, and unlocking its secrets could enable the development of more reliable and efficient RNA-based technologies,” he said.
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