A novel N4,N4-dimethylcytidine in the archaeal ribosome enhances hyperthermophily

• 成果类型: Article
• 署名作者: Fluke, Kristin A.; Dai, Nan; Wolf, Eric J.; Fuchs, Ryan T.; Ho, P. Shing; Talbott, Victoria; Elkins, Liam; Tsai, Yueh - Lin; Schiltz, Jackson; Febvre, Hallie P.; Czarny, Ryan; Robb, G. Brett; Correa Jr, Ivan R.; Santangelo, Thomas J.
• 署名单位: Colorado State University System; Colorado State University Fort Collins; Colorado State University System; Colorado State University Fort Collins; New England Biolabs
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10421
• DOI: 10.1073/pnas.2405999121
• 发表日期: 2024-11-05
• 关键词: thermus-thermophilus; transfer-rna; thermococcus-kodakarensis; structural basis; decoding center; methyltransferase; mechanism; methylation

摘要

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, N 4, N 4- dimethylcytidine (m42C), 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 m42C whose function is critical for hyperthermophilic growth. m42C is synthesized by the activity of a unique family of RNA methyltransferase containing a Rossman-fold that targets only intact ribosomes. The phylogenetic distribution of the newly identified m42C synthase family implies that m42C is biologically relevant in each domain. Resistance of m42C to bisulfite- driven deamination suggests that efforts to capture m5C profiles via bisulfite sequencing are also capturing m4 2 C.