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

DNA包含生命所必需的信息，准确阅读这种材料对于适应不断变化的环境至关重要。这是通过一个被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）是细胞中负责大多数转录的分子机器。它包含一个称为c端结构域（CTD）的扩展区域。CTD对于所有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。这种活性取决于CTD上改性的及时沉积和去除。例如，转录开始时的CTD修饰状态与转录结束时的状态不同，这使得RNAPII可以在转录过程的不同阶段招募特定的因子。CTD通过细胞中多种酶的协同作用进行修饰，包括Fcp1和Cdk8。Fcp1通常通过去除转录结束后所有的CTD修饰来循环RNAPII。这个RNAPII可以被Cdk8靶向，通过过早地修饰它的CTD来阻止它开始额外的转录。因此，Fcp1和Cdk8在调控RNAPII的转录可用性中发挥重要作用。******先前的研究表明，缩短CTD会导致基因组信息的错误读取、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都观察到这些影响，但其他影响仅限于较小的子集，这改变了我们的观点，即RNAP-CTD仅具有一般功能，能够以特定方式整合调节信号。我们最近对Fcp1的研究也得到了类似的结果，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，我们提出梳理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，以确保正确读取遗传信息。**

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. **