发育基因表达、衰老和疾病中的转录延伸控制。
Transcriptional elongation control in developmental gene expression, aging, and disease.
发表日期:2023 Oct 26
作者:
Yuki Aoi, Ali Shilatifard
来源:
MOLECULAR CELL
摘要:
RNA 聚合酶 II (RNA Pol II) 转录的延伸阶段对于后生动物响应发育和环境线索而调节基因表达至关重要。转录延伸失调与发育缺陷以及疾病和衰老过程有关。数十年的遗传和生化研究已经精心鉴定和表征了调节 RNA Pol II 延伸的一系列因素。这篇综述总结了利用基因工程技术探测体内伸长因子功能的最新发现。我们通过调和早期生化证据和最近的体内研究的矛盾结果,提出了该加速场中伸长控制的修订模型。我们讨论延伸因子如何调节启动子近端 RNA Pol II 暂停释放、转录延伸率和持续性、RNA Pol II 稳定性和 RNA 加工,以及这些过程的扰动如何与发育障碍、神经退行性疾病、癌症和衰老相关。 © 2023。由爱思唯尔公司出版。
The elongation stage of transcription by RNA polymerase II (RNA Pol II) is central to the regulation of gene expression in response to developmental and environmental cues in metazoan. Dysregulated transcriptional elongation has been associated with developmental defects as well as disease and aging processes. Decades of genetic and biochemical studies have painstakingly identified and characterized an ensemble of factors that regulate RNA Pol II elongation. This review summarizes recent findings taking advantage of genetic engineering techniques that probe functions of elongation factors in vivo. We propose a revised model of elongation control in this accelerating field by reconciling contradictory results from the earlier biochemical evidence and the recent in vivo studies. We discuss how elongation factors regulate promoter-proximal RNA Pol II pause release, transcriptional elongation rate and processivity, RNA Pol II stability and RNA processing, and how perturbation of these processes is associated with developmental disorders, neurodegenerative disease, cancer, and aging.Copyright © 2023. Published by Elsevier Inc.