A novel 4,4-dimethylcytidine in the archaeal ribosome enhances hyperthermophily.

Ribosome structure and activity are challenged at high temperatures, often demanding modifications to ribosomal RNAs (rRNAs) to retain translation fidelity. LC-MS/MS, bisulfite-sequencing, and high-resolution cryo-EM structures of the archaeal ribosome identified an RNA modification, 4,4-dimethylcytidine (mC), at the universally conserved C918 in the 16S rRNA helix 31 loop. Here, we characterize and structurally resolve a class of RNA methyltransferase that generates mC whose function is critical for hyperthermophilic growth.

The extensive mC epitranscriptome of Thermococcus kodakarensis is generated by a suite of RNA methyltransferases that support thermophily.

RNAs are often modified to invoke new activities. While many modifications are limited in frequency, restricted to non-coding RNAs, or present only in select organisms, 5-methylcytidine (mC) is abundant across diverse RNAs and fitness-relevant across Domains of life, but the synthesis and impacts of mC have yet to be fully investigated. Here, we map mC in the model hyperthermophile, Thermococcus kodakarensis.

Tetraether archaeal lipids promote long-term survival in extreme conditions.

The sole unifying feature of the incredibly diverse Archaea is their isoprenoid-based ether-linked lipid membranes. Unique lipid membrane composition, including an abundance of membrane-spanning tetraether lipids, impart resistance to extreme conditions. Many questions remain, however, regarding the synthesis and modification of tetraether lipids and how dynamic changes to archaeal lipid membrane composition support hyperthermophily.