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

DNA包含生命所需的信息，准确阅读这些材料对于适应不断变化的环境是必不可少的。这是通过一个称为转录的过程来完成的，在这个过程中，细胞选择要读取的遗传信息。RNA聚合酶II(RNAPII)是负责细胞内大部分转录的分子机器。它包含一个称为C-末端结构域(CTD)的扩展区域。CTD对于所有依赖RNAPII的转录都很重要，因为它是一个招募这一过程所需辅助因子的平台。这一活动有赖于及时沉积和去除对CTD的修饰。例如，转录开始时的CTD修饰状态与转录结束时的不同，使RNAPII能够在转录过程的不同阶段招募特定的因子。CTD是通过细胞内包括Fcp1和CDK8在内的许多酶的协调作用来修饰的。Fcp1通常通过在转录结束后移除所有CTD修饰来循环RNAPII。然后，CDK8可以通过过早修改其CTD来针对该RNAPII，阻止其启动额外的几轮转录。因此，Fcp1和CDK8在调节RNAPII的转录可用性方面发挥着重要作用。*先前的研究表明，缩短CTD会导致对基因组信息的不正确读取，削弱对不断变化的环境的适应能力，改变CTD修饰模式，并改变转录过程中必要因子的招募。有趣的是，上述工作还表明，虽然其中一些影响在所有转录单位中都能观察到，但其他影响仅限于较小的子集，从而改变了我们对RNAP-CTD专门执行一般功能的看法，使其能够以特定的方式整合调控信号。我们最近对Fcp1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，因为它与高温和盐条件的适应有关。在这里，我们建议梳理RNAPII-CTD和Fcp1的一般功能和特定功能，并确定与它们沟通的因素和途径，以确保正确阅读遗传信息。**

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. **