假尿苷
癌变
生物
癌症研究
胶质母细胞瘤
转移RNA
长非编码RNA
基因敲除
核糖核酸
遗传学
基因
作者
Qi Cui,Kailin Yin,Qian Zhang,Ye Peng,Xianwei Chen,Jianfei Chao,Haowei Meng,Jiangbo Wei,Daniel Röth,Li Li,Yue Qin,Guihua Sun,Mingzi Zhang,Jeremy Klein,Marvin Huynhle,Cheng Wang,Leying Zhang,Behnam Badie,Markus Kalkum,Chuan He,Chengqi Yi,Yanhong Shi
出处
期刊:Nature cancer
[Springer Nature]
日期:2021-08-16
卷期号:2 (9): 932-949
被引量:81
标识
DOI:10.1038/s43018-021-00238-0
摘要
Pseudouridine is the most frequent epitranscriptomic modification. However, its cellular functions remain largely unknown. Here, we show that pseudouridine synthase 7 (PUS7) is highly expressed in glioblastoma versus normal brain tissues, and high PUS7 expression levels are associated with worse survival in patients with glioblastoma. PUS7 expression and catalytic activity are required for glioblastoma stem cell (GSC) tumorigenesis. Mechanistically, we identify PUS7 targets in GSCs through small RNA pseudouridine sequencing and show that pseudouridylation of PUS7-regulated transfer RNA is critical for codon-specific translational control of key regulators of GSCs. Moreover, we identify chemical inhibitors for PUS7 and show that these compounds prevent PUS7-mediated pseudouridine modification, suppress tumorigenesis and extend the life span of tumor-bearing mice. Overall, we identify an epitranscriptomic regulatory mechanism in glioblastoma and provide preclinical evidence of a potential therapeutic strategy for glioblastoma. Shi and colleagues show that PUS7 controls tRNA pseudouridylation and codon-specific translation to fuel glioblastoma tumorigenesis, and discover a PUS7 inhibitor that delays tumor growth in glioblastoma models.
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