低酸素環境においてRNAの骨格がメチル化される!～立体選択的なRNAの修飾がリボソームを活性化する～

2025-12-12 東京大学

概要図:新規rRNA修飾が嫌気環境特異的に大腸菌の生育を促進する

<関連情報>

• https://www.t.u-tokyo.ac.jp/press/pr2025-12-12-001
• https://www.t.u-tokyo.ac.jp/hubfs/press-release/2025/1212/001/text.pdf
• https://www.sciencedirect.com/science/article/pii/S1097276525009359

低酸素誘導性リボソームRNAのペプチジルトランスフェラーゼ中心における修飾は細菌の嫌気性増殖に寄与する Hypoxia-induced ribosomal RNA modifications in the peptidyl-transferase center contribute to anaerobic growth of bacteria

Kensuke Ishiguro, Karin Midorikawa, Naoki Shigi, Satoshi Kimura, Aivar Liiv, Takeshi Yokoyama, Takuhiro Ito, Mikako Shirouzu, Jaanus Remme, Kenjyo Miyauchi, Tsutomu Suzuki
Molecular Cell  Available online: 10 December 2025
DOI:https://doi.org/10.1016/j.molcel.2025.11.018

Highlights

• Discovery of RNA backbone modifications in bacterial rRNAs under hypoxia
• RlmX, a cobalamin-dependent radical SAM MTase, installs the hypoxic methylations
• Two hypoxic methylations and 5-hydroxycytidine contribute to anaerobic growth
• The hypoxic modifications stabilize PTC and promote peptide bond formation

Summary

Ribosomal RNAs (rRNAs) contain various modifications that play critical roles in ribosome assembly and function. Here, we discovered two stereoselective methylations of the rRNA backbone in the peptidyl-transferase center (PTC) of the 50S subunit of Escherichia coli cultured under anaerobic conditions. Methylation occurs at carbon 5′(S) of ribose moieties of dihydrouridine at position 2449 (D^5Sm2449) and 2′-O-metylcytidine at position 2498 (Cm^5Sm2498). We identified the rlmX gene, encoding a cobalamin-dependent radical S-adenosylmethionine (SAM) methyltransferase responsible for these methylations. Intriguingly, D^5Sm2449, Cm^5Sm2498, and 5-hydroxycytidine (ho⁵C2501) in the PTC were elevated under anaerobic growth conditions. A double knockout strain lacking rlmX and rlhA (responsible for ho⁵C2501) impaired anaerobic growth. Biochemical studies showed that these rRNA modifications stimulate protein synthesis. The cryoelectron microscopy (cryo-EM) structure of the ribosome indicated that these hypoxia-induced modifications stabilize the P-site and the PTC. These findings demonstrate that ribosomes are activated by hypoxia-induced modifications to enhance translational capability and thereby survival, under anaerobic conditions.