魏茨曼科学研究所Schraga Schwartz小组宣布他们发现了泛修饰谱有助于对温度调节核糖体表转录组进行交叉进化解剖。相关论文于2025年10月22日发表在《细胞》杂志上。
课题组人员开发了Pan-Mod-seq，允许在数十个样本中并行推断16种不同的修改。该研究团队将Pan-Mod-seq应用于14种跨越所有生命领域的物种的RNA，这些物种在高度多样化的条件下培养。虽然在中温菌中很少发生动态修饰，但在极端嗜热菌中，约50%的修饰是动态的。该课题组人员剖析了m5C-ac4C串联修饰的一个保守模块的生物发生和功能，该模块在高温下共同诱导，通过内在受温度调节的酶，在更高温度下生长。野生型（WT）和酶缺陷古菌核糖体的冷冻电镜（cryo-EM）结构揭示了反复发生的分子相互作用，通过这种相互作用，它们赋予了结构稳定性，生物物理学研究证明了它们的协同热稳定作用。他们的发现系统地剖析了rRNA修饰的可塑性，并为研究健康和疾病中的rRNA表转录组铺平了道路。
据了解，核糖体RNA （rRNA）是核糖体的核心，被广泛的化学修饰。技术上的挑战阻碍了对rRNA修饰及其动力学的系统剖析。
附：英文原文
Title: Pan-modification profiling facilitates a cross-evolutionary dissection of the thermoregulated ribosomal epitranscriptome
Author: Miguel A. Garcia-Campos, Joe Georgeson, Ronit Nir, Robert Reichelt, Kristin A. Fluke, Donna Matzov, Vinithra Iyer, Brett W. Burkhart, Lauren Lui, Anatoly Kustanovich, Felix Grünberger, Supuni Thalalla-Gamage, Shereen A. Howpay-Manage, Milan Gerovac, Nicolas Alexandre, Yuko Nobe, Jakub S. Nowak, Manoj Perera, Alexander Apostle, Shiyue Fang, Sebastian Glatt, Ghil Jona, Sébastien Ferreira-Cerca, Jrg Vogel, Masato Taoka, Jordan L. Meier, Eric Westhof, Thomas J. Santangelo, Dina Grohmann, Moran Shalev-Benami, Schraga Schwartz
Issue&Volume: 2025-10-22
Abstract: Ribosomal 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, ～50% of modifications are dynamic. We dissect the biogenesis and function of a conserved module of tandem m5C-ac4C 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.
DOI: 10.1016/j.cell.2025.09.014
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01082-7