9qf5
Structure of P. furiosus 70S ribosome grown at 102deg
Structural highlights
FunctionPublication Abstract from PubMedRibosomal RNA (rRNA) constitutes the core of ribosomes and is extensively chemically modified. Technical challenges have precluded systematically dissecting rRNA modifications and their dynamics. We develop Pan-Mod-seq, permitting inference of 16 distinct modifications across dozens of samples in parallel. We applied Pan-Mod-seq to RNA from 14 species spanning all domains of life, cultured under highly diverse conditions. While dynamic modifications are rare in mesophiles, in extreme hyperthermophiles, approximately 50% of modifications are dynamic. We dissect the biogenesis and function of a conserved module of tandem m(5)C-ac(4)C modifications, co-induced at high temperatures, via enzymes intrinsically regulated by temperature and required for growth at higher temperatures. Cryo-electron microscopy (cryo-EM) structures of ribosomes from wild-type (WT) and enzyme-deficient archaea reveal recurrent molecular interactions through which they confer structural stability, and biophysical studies demonstrate their synergistic thermostabilizing role. Our findings systematically dissect rRNA modification plasticity and pave the way for surveying the rRNA epitranscriptome in health and disease. Pan-modification profiling facilitates a cross-evolutionary dissection of the thermoregulated ribosomal epitranscriptome.,Garcia-Campos MA, Georgeson J, Nir R, Reichelt R, Fluke KA, Matzov D, Iyer V, Burkhart BW, Lui L, Kustanovich A, Grunberger F, Thalalla-Gamage S, Howpay-Manage SA, Gerovac M, Alexandre N, Nobe Y, Nowak JS, Perera M, Apostle A, Fang S, Glatt S, Jona G, Ferreira-Cerca S, Vogel J, Taoka M, Meier JL, Westhof E, Santangelo TJ, Grohmann D, Shalev-Benami M, Schwartz S Cell. 2025 Oct 22:S0092-8674(25)01082-7. doi: 10.1016/j.cell.2025.09.014. PMID:41130207[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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