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 和生存而转录的过早停止可能会产生截短的， 有缺陷的转录本;停止太晚可能会破坏下游的调节 基因在相同的方向，并产生反义RNA对基因在相同的方向， 相反的方向。任何一种结果都会对基因表达产生重大影响。 表情因此，转录终止缺陷是导致转录终止的原因并不奇怪。 与各种人类疾病相关的疾病，如血栓形成倾向、地中海贫血和 癌我们之前在最近的一项研究中证明， 帽结合蛋白复合物与抗终止因子Np 13 p共同发挥功能 来调节转录终止。在这个项目中，我将继续阐明 出芽模式生物中真核转录终止的机制 酵母使用遗传和分子生物学方法的组合。我的研究将 重点关注Np 13 p对真核生物转录终止的调控， 真核生物转录终止与RNA监视的功能偶联。为 第一部分，阐述Np 13 p的翻译后修饰对Np 13 p表达的影响， 抗终止活性。在第二部分，我将探讨细胞机器如何 转录终止和RNA监视在功能上与每个 其他.特别是，我将研究核外泌体的共转录募集 Rrp6p。由于转录终止的根本重要性， 从酵母到人的转录终止机制的保守程度， 我们的发现将对人类疾病产生重要影响， 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.