神经母细胞瘤RAS病毒癌基因同源物
非翻译区
翻译(生物学)
信使核糖核酸
三素数非翻译区
生物
神经母细胞瘤
癌症研究
分子生物学
细胞生物学
基因
遗传学
细胞培养
突变
克拉斯
作者
Sumirtha Balaratnam,Zachary R Torrey,David Calabrese,Michael T. Banco,Kamyar Yazdani,Xiao Liang,Christopher R. Fullenkamp,Srinath Seshadri,Ronald Holewinski,Þorkell Andrésson,A.R. Ferré-D′Amaré,Danny Incarnato,John S. Schneekloth
标识
DOI:10.1016/j.chembiol.2023.05.004
摘要
Summary
Neuroblastoma RAS (NRAS) is an oncogene that is deregulated and highly mutated in cancers including melanomas and acute myeloid leukemias. The 5′ untranslated region (UTR) (5′ UTR) of the NRAS mRNA contains a G-quadruplex (G4) that regulates translation. Here we report a novel class of small molecule that binds to the G4 structure located in the 5′ UTR of the NRAS mRNA. We used a small molecule microarray screen to identify molecules that selectively bind to the NRAS-G4 with submicromolar affinity. One compound inhibits the translation of NRAS in vitro but showed only moderate effects on the NRAS levels in cellulo. Rapid Amplification of cDNA Ends and RT-PCR analysis revealed that the predominant NRAS transcript does not possess the G4 structure. Thus, although NRAS transcripts lack a G4 in many cell lines the concept of targeting folded regions within 5′ UTRs to control translation remains a highly attractive strategy.
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