The RNAPII-CTD at the nexus of general and gene-specific regulation of transcription

RNAPII-CTD 处于一般转录调控和基因特异性转录调控的关系中

• 批准号: RGPIN-2016-04297
• 负责人: Kobor, Michael
• 金额: $ 3.21万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688818
• 关键词: RNAPII; CTD; nexus; general; gene

DNA contains the information necessary for life and accurate reading of this material is essential to adapt to changing environments. This is accomplished though a processed called transcription, during which the cell selects the genetic information to be read. RNA Polymerase II (RNAPII) is the molecular machine responsible for most transcription in the cell. It contains an extended region called the C-terminal domain (CTD). The CTD is important for all RNAPII-dependent transcription, given that it function as a platform for recruiting auxiliary factors required for this process. This activity is dependent on timely deposition and removal of modifications on the CTD. For example, the CTD modification status at the beginning of transcription differs from that of the end, allowing RNAPII to recruit specific factors at different stages of the process. The CTD is modified through the coordinated action of a number of enzymes in the cell, including Fcp1 and Cdk8. Fcp1 generally functions in recycling RNAPII by removing all CTD modifications following the end of transcription. This RNAPII can then be targeted by Cdk8, which blocks it from starting additional rounds of transcription, by prematurely modifying its CTD. As such, Fcp1 and Cdk8 play important roles in regulating the availability of RNAPII for transcription. ******Previously it was shown that shortening the CTD results in incorrect reading of genomic information, impaired ability to adapt to changing environments, altered CTD modification patters, and altered recruitment of factors necessary during transcription. Interestingly, the work described above also showed that while some of these effects were observed across all transcriptional units, others were confined to a smaller subset, switching our view of the RNAP-CTD as exclusively performing general functions, to being able to integrate regulatory signals in a specific manner. Our recent investigation of Fcp1 yielded similar findings as it revealed specific functions during transcription as it relates to the adaptation to high temperature and salt conditions. Here, we propose to tease apart general vs. specific functions of the RNAPII-CTD and Fcp1, and to identify factors and pathways that communicate with them to ensure correct reading of genetic information. **

DNA包含生命所必需的信息，准确阅读这些材料对于适应不断变化的环境至关重要。这是通过一个称为转录的过程来完成的，在此过程中，细胞选择要读取的遗传信息。RNA聚合酶II（RNAPII）是负责细胞中大部分转录的分子机器。它包含一个称为C-末端结构域（CTD）的延伸区域。CTD对所有RNAPII依赖性转录都很重要，因为它是招募该过程所需辅助因子的平台。该活动取决于CTD上修改的及时沉积和移除。例如，转录开始时的CTD修饰状态与结束时的CTD修饰状态不同，这使得RNAPII能够在该过程的不同阶段招募特定的因子。CTD通过细胞中许多酶的协调作用进行修饰，包括Fcp 1和Cdk 8。Fcp 1通常通过在转录结束后去除所有CTD修饰来回收RNAPII。然后，这种RNAPII可以被Cdk 8靶向，Cdk 8通过过早地修饰其CTD来阻止它开始额外的转录轮次。因此，Fcp 1和Cdk 8在调节RNAPII转录的可用性方面发挥重要作用。** 以前的研究表明，缩短CTD会导致基因组信息的不正确阅读、适应环境变化的能力受损、CTD修饰模式改变以及转录过程中必要因子的募集改变。有趣的是，上述工作还表明，虽然在所有转录单位中观察到了其中一些效应，但其他效应仅限于较小的子集，从而将我们认为RNAP-CTD仅执行一般功能的观点转变为能够以特定方式整合调控信号。我们最近对Fcp 1的研究也得到了类似的发现，因为它揭示了转录过程中的特定功能，因为它与适应高温和盐条件有关。在这里，我们建议梳理分开RNAPII-CTD和Fcp 1的一般与特定功能，并确定与它们通信的因素和途径，以确保正确的遗传信息的阅读。**