Archaea can take the heat. Now we know one reason why. Tokyo Metropolitan University researchers have found a natural sulfur-based change in the RNA backbone of these heat-loving microbes. This is not a lab trick. It happens in nature.
For years, scientists used artificial thiophosphate tweaks to make RNA drugs tougher. But this team showed that archaea already use a similar sulfur swap in their own ribosomal RNA (rRNA) and transfer RNA (tRNA). According to an official announcement by Tokyo Metropolitan University, the change swaps out a non-bridging oxygen atom in the RNA backbone for sulfur. The team found these marks in both rRNA and tRNA from several archaeal species.
All naturally occurring RNA phosphorothioate bonds identified in this study exhibited a strict R-stereospecific configuration, distinguishing them from the non-specific or synthetic mixtures commonly produced in the laboratory.
Enzymes at the heart of the process
The study, published in Cell on September 18, 2026, names two new enzymes: Esti-A and Esti-B. These are the workers that add the sulfur. Knock out either one, and archaea can’t handle high heat. Some die. Others grow much slower. The modified links cluster near the rRNA’s peptide transfer site and help keep tRNA stable. This is crucial for making proteins when things get hot. The number of these sulfur swaps changes with growth temperature and sulfur in the medium. rRNA modifications pile up near mRNA decoding spots and the peptidyl transferase center, as detailed in the university's research summary.
This was not a solo effort. Teams from Israel, the USA, Germany, France, Poland, Austria, and more joined in. Funding came from the Japan Society for the Promotion of Science and the TMU GAP Fund. The group mapped these changes down to single nucleotides. They used advanced sequencing and mass spectrometry. The marks showed up in conserved rRNA and tRNA regions across many archaeal species, as reported in a detailed analysis by vbio.de.
Researchers identified a new family of enzymes, Esti, including Esti-A and Esti-B; loss of their function led to either complete lethality in some archaea or temperature-dependent growth retardation.
What this means for RNA medicine
This isn’t just a basic science win. The discovery gives RNA drug makers a new playbook. Nature’s own sulfur swap could help build tougher, more reliable RNA medicines. The study shows how life stabilizes RNA in brutal conditions. That’s a lesson for both biology and biotech.
The evidence is clear. RNA’s chemistry is more varied—and more important—than many thought. Finding these natural thiophosphate marks and the enzymes that make them changes the game. It will shape how scientists design RNA drugs and how they think about life’s ability to survive. Tokyo Metropolitan University said in an official statement that this work proves chemical tweaks hit not just RNA bases, but the backbone too. That opens the door to programmable tools for building stronger nucleic acids.
