7XNX

High resolution cry-EM structure of the human 80S ribosome from SNORD127+/+ Kasumi-1 cells

これはPDB形式変換不可エントリーです。

7XNX の概要

• エントリーDOI: 10.2210/pdb7xnx/pdb
• EMDBエントリー: 33329
• 分子名称: 28S rRNA, 60S ribosomal protein L7a, 60S ribosomal protein L9, ... (83 entities in total)
• 機能のキーワード: ribosome, rrna ribomethylome
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 81
• 化学式量合計: 3862762.69

構造登録者

Cheng, J.,Beckmann, R. (登録日: 2022-04-30, 公開日: 2023-04-05, 最終更新日: 2025-02-12)

主引用文献

Zhou, F.,Aroua, N.,Liu, Y.,Rohde, C.,Cheng, J.,Wirth, A.K.,Fijalkowska, D.,Gollner, S.,Lotze, M.,Yun, H.,Yu, X.,Pabst, C.,Sauer, T.,Oellerich, T.,Serve, H.,Rollig, C.,Bornhauser, M.,Thiede, C.,Baldus, C.,Frye, M.,Raffel, S.,Krijgsveld, J.,Jeremias, I.,Beckmann, R.,Trumpp, A.,Muller-Tidow, C.
A Dynamic rRNA Ribomethylome Drives Stemness in Acute Myeloid Leukemia.
Cancer Discov, 13:332-347, 2023

PubMed Abstract: The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, and functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O-methylation regulate leukemia stem cell (LSC) activity in vivo. A comprehensive analysis of the rRNA 2'-O-methylation landscape of 94 patients with acute myeloid leukemia (AML) revealed dynamic 2'-O-methylation specifically at exterior sites of ribosomes. The rRNA 2'-O-methylation pattern is closely associated with AML development stage and LSC gene expression signature. Forced expression of the 2'-O-methyltransferase fibrillarin (FBL) induced an AML stem cell phenotype and enabled engraftment of non-LSC leukemia cells in NSG mice. Enhanced 2'-O-methylation redirected the ribosome translation program toward amino acid transporter mRNAs enriched in optimal codons and subsequently increased intracellular amino acid levels. Methylation at the single site 18S-guanosine 1447 was instrumental for LSC activity. Collectively, our work demonstrates that dynamic 2'-O-methylation at specific sites on rRNAs shifts translational preferences and controls AML LSC self-renewal.

PubMed: 36259929
DOI: 10.1158/2159-8290.CD-22-0210

実験手法

ELECTRON MICROSCOPY (2.7 Å)