Regulation of transcription termination and its link in mRNA surveillance

转录终止的精确调控对细胞生长至关重要 和生存。而过早停止转录可能会产生截断和 有缺陷的转录；停止得太晚可能会扰乱下游的调控 在同一方向的基因，并产生针对基因的反义RNA 方向相反。任何一种结果都会对基因产生重大影响 表情。因此，转录终止缺陷是因果关系也就不足为奇了。 与各种人类疾病有关，如血栓形成症、地中海贫血和 癌症。我们之前在最近的一项研究中证明了 帽结合蛋白复合体与抗终末因子Npl3p的联合作用 调节转录终止。在这个项目中，我将继续阐明 发芽模式生物真核转录终止机制的研究 酵母使用遗传和分子生物学相结合的方法。我的学习将会 Npl3p和Npl3p对真核细胞转录终止的调控 真核转录终止与RNA监测的功能耦合。为 第一部分，界定Npl3p的翻译后修饰对其的影响 反堕胎活动。对于第二部分，我将探索细胞机械是如何 转录终止和RNA监视在功能上是相互耦合的 其他的。特别是，我将研究核外切体的共转录招募 Rrp6p。因为转录终止的基本重要性和高 从酵母到人类的转录终止机制的保守度， 我们的发现将对人类疾病产生重要的影响 转录终止缺陷。

Precise regulation of transcription termination is essential to cellular growth and survival. While premature stopping of transcription may produce truncated and defective transcripts; stopping too late may disrupt the regulation of downstream genes in the same orientation and generate antisense RNA against genes in the opposite orientation. Either outcome would have significant impact on gene expression. Thus, it is not surprising that transcription termination defects are causally associated with various human diseases, such as thrombophilia, thalassemia and cancer. We have previously demonstrated in a recent study that the mRNA cap-binding protein complex functions in conjunction with antitermination factor Npl3p to regulate transcription termination. In this project, I will continue to shed light on the mechanisms of eukaryotic transcription termination in the model organism of budding yeast using a combination of genetic and molecular biological methods. My study will focus on the regulation of eukaryotic transcription termination through Npl3p and the functional coupling of eukaryotic transcription termination with RNA surveillance. For the first part, I will define the influence of post-translational modification of Npl3p on its antitermination activity. For the second part, I will explore how cellular machineries of transcription termination and RNA surveillance are functionally coupled with each other. Particularly, I will investigate cotranscriptional recruitment of nuclear exosome Rrp6p. Because of the fundamental importance of transcription termination and high degree of conservation of transcription termination machineries from yeast to human, our findings will have important implications in human diseases caused by transcription termination defects.