Low RNA stability signifies strong expression regulatability of tumor suppressors

被引：3
作者：
Gao, Xinlei [1 ,2 ,3 ]
Yi, Yang [4 ]
Lv, Jie [3 ]
Li, Yanqiang [1 ,2 ,3 ]
Arulsamy, Kulandaisamy [1 ,2 ]
Babu, Sahana Suresh [3 ]
Bruno, Ivone [3 ]
Zhang, Lili [1 ]
Cao, Qi [4 ]
Chen, Kaifu [1 ,2 ,3 ,5 ]
机构：
[1] Boston Childrens Hosp, Dept Cardiol, Basic & Translat Res Div, Boston, MA 02115 USA
[2] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA
[3] Methodist Hosp Syst, Houston Methodist Res Inst, Houston, TX 77030 USA
[4] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA
[5] Dana Farber Harvard Canc Ctr, Prostate Canc Program, Boston, MA 02115 USA
来源：
NUCLEIC ACIDS RESEARCH | 2023年 / 51卷 / 21期
关键词：
GENE-EXPRESSION; SUPER-ENHANCERS; CELL IDENTITY; CANCER; TRANSCRIPTION; METHYLATION; TRANSLATION; MUTATIONS; HALLMARKS; PROTEINS;
D O I：
10.1093/nar/gkad838
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
RNA expression of a gene is determined by not only transcriptional regulation, but also post-transcriptional regulation of RNA decay. The precise regulation of RNA stability in the cell plays an important role in normal development. Dysregulation of RNA stability can lead to diseases such as cancer. Here we found tumor suppressor RNAs tended to decay fast in normal cell types when compared with other RNAs. Consistent with a negative effect of m6A modification on RNA stability, we observed preferential deposition of m6A on tumor suppressor RNAs. Moreover, abundant m6A and fast decay of tumor suppressor RNAs both tended to be further enhanced in prostate cancer cells relative to normal prostate epithelial cells. Further, knockdown of m6A methyltransferase METTL3 and reader YTHDF2 in prostate cancer cells both posed stronger effect on tumor suppressor RNAs than on other RNAs. These results indicated a strong post transcriptional expression regulatability mediated by abundant m6A modification on tumor suppressor RNAs. Graphical Abstract
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页码：11534 / 11548
页数：15
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