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Functional screens identify coordinators of RNA molecule birth, life, and death as targetable cancer vulnerabilities.
Current Opinion in Genetics & Development ( IF 3.7 ) Pub Date : 2019-05-20 , DOI: 10.1016/j.gde.2019.04.003
Christian J Braun 1 , Michael T Hemann 2
Affiliation  

RNA molecules are subject to a complex co-transcriptional and post-transcriptional life cycle, controlled at all stages by RNA binding proteins (RBPs) and non-coding RNAs that influence mRNA stability, splicing, localization, and decay. Together with mechanisms regulating the process of transcription itself, non-coding RNAs and RBPs contribute to a model of para-transcriptional coordination of gene expression, which is utilized during normal tissue physiology and cancer development in order to execute complex gene expression programs. Several key regulators of RNA biology, such as certain splice factors, represent bona fide cancer vulnerabilities, but our understanding of these processes is still far away from being comprehensive. Genetic forward screens utilizing technologies such as transposons, RNAi and CRISPR aid the field in rapidly establishing functional phenotypes and genetic cancer cell addictions. This review focuses on four individual regulatory gene expression processes governed by regulators of the RNA life cycle, the impact of functional genomics on streamlining the discovery process and the role of such mechanisms in tumor biology.

中文翻译:

功能筛选将RNA分子出生,生活和死亡的协调员识别为可靶向的癌症易感性。

RNA分子处于复杂的共转录和转录后生命周期,在所有阶段都受RNA结合蛋白(RBP)和影响mRNA稳定性,剪接,定位和衰变的非编码RNA的控制。与调节转录过程本身的机制一起,非编码RNA和RBP促进了基因表达的超转录协调模型,该模型在正常组织生理学和癌症发展过程中用于执行复杂的基因表达程序。RNA生物学的几个关键调控因子(例如某些剪接因子)代表了真正的癌症脆弱性,但我们对这些过程的理解还远远不够全面。利用转座子,RNAi和CRISPR帮助该领域快速建立功能表型和遗传性癌细胞成瘾。这篇综述集中在四个独立的调节基因表达过程,这些过程由RNA生命周期的调节器控制,功能基因组学对简化发现过程的影响以及这种机制在肿瘤生物学中的作用。
更新日期:2019-05-20
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