期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 179, 期 12, 页码 2868-2889出版社
WILEY
DOI: 10.1111/bph.15604
关键词
A-to-I-editing; cancer; epitranscriptomics; pseudouridine; RNA methylation; small-molecule inhibitors; therapy
资金
- Instituto de Salud Carlos III
- European Regional Development Funds (ERDF/FEDER) a way to build Europe [PI15/00638, PI18/00910]
- Health Department PERIS-project [SLT/002/16/00374]
- AGAUR of the Catalan Government (Generalitat de Catalunya) [2017SGR1080]
- Ministerio de Ciencia e Innovacion (MCI)
- European Regional Development Fund (ERDF) [RTI2018-094049-B-I00]
- Cellex Foundation
- 'la Caixa' Banking Foundation [LCF/PR/GN18/51140001]
- Agencia Estatal de Investigacion (AEI)
Epitranscriptomics is a burgeoning field that studies biochemical modifications of RNA, with a focus on both normal cell fate and the development of diseases such as cancer. The challenge now is to identify mechanisms within epitranscriptomics that can be targeted effectively by drugs. Despite facing challenges in chemical biology and drug development, there is still great potential for targeted-RNA to benefit clinical outcomes.
Epitranscriptomics is an exciting emerging area that studies biochemical modifications of RNA. The field has been opened up by the technical efforts of the last decade to characterize and quantify RNA modifications, and this has led to a map of post-transcriptional RNA marks in normal cell fate and development. However, the scientific interest has been fuelled by the discovery of aberrant epitranscriptomes associated with human diseases, mainly cancer. The challenge is now to see whether epitrancriptomics offers mechanisms that can be effectively targeted by low MW compounds and are thus druggable. In this review, we will describe the principal RNA modifications (with a focus on mRNA), summarize the latest scientific evidence of their dysregulation in cancer and provide an overview of the state-of-the-art drug discovery to target the epitranscriptome. Finally, we will discuss the principal challenges in the field of chemical biology and drug development to increase the potential of targeted-RNA for clinical benefit.
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