权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Transcription elongation processivity: backtracked complexes formation and resolution

转录延伸持续性：回溯复合物的形成和解析

基本信息

批准号：
BB/F013558/1
负责人：
Nikolay Zenkin
金额：
$ 49.33万
依托单位：
Newcastle University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF013558%2F1
关键词：
Transcription elongation processivity backtracked complexes

项目摘要

Transcription is the first and the most heavily regulated step of gene expression. Many internal and external signals, such as sequences in the template, proteins bound to the template, etc., may influence the movement of RNA polymerase along DNA. These signals can slow down or even stall transcription, which leads to the formation of inactive backtracked complexes. Backtracked complex forms due to backward movement of RNA polymerase along the DNA template, which leaves the 3' end of the RNA out of the active centre and thus inactivates the elongation complex, e.g. leads to the premature termination of transcription. More importantly backtracked complexes are obstacles for different cellular machineries that work on RNA or DNA. Thus, there should have been mechanisms invented by cells to 'rescue' or 'resolve' these harmful complexes. The proposed mechanism of resolution via unassisted transcript hydrolysis by RNA polymerase active centre was found to be too inefficient. Cleavage factors that increase this hydrolytic activity were shown to be dispensable for cells. Thus, the mechanisms ensuring efficient resolution of backtracked complexes are still poorly understood. Here I propose a new factor-independent mechanism for the resolution of backtracked complexes that would explain how they can be efficiently resolved during transcription. The proposal is based on hypothesises (supported by preliminary results) that: i) resolution of backtracked complexes occurs at specific sites on the template DNA, at which transcript cleavage reactions are highly increased; ii) the transcript itself assists cleavage in the back-tracked complexes, thus reactivating them. We are going to test these hypothesises, and further investigate mechanisms of backtracking and rescue from it. The research of this proposal will also improve understanding of the structure and properties of transcription elongation complexes, and will shed light on the mechanisms of transcriptional pausing and termination.

转录是基因表达的第一步，也是最受调控的一步。许多内部和外部信号，如模板中的序列、与模板结合的蛋白质等，可能影响RNA聚合酶沿着DNA的运动。这些信号可以减慢甚至停止转录，这导致形成无活性的回溯复合物。由于RNA聚合酶沿着DNA模板的向后移动而形成回溯复合物，这使RNA的3'末端离开活性中心，从而使延伸复合物失活，例如导致转录的过早终止。更重要的是，回溯复合物是作用于RNA或DNA的不同细胞机制的障碍。因此，应该有细胞发明的机制来“拯救”或“解决”这些有害的复合物。提出的通过RNA聚合酶活性中心的无辅助的转录物水解的拆分机制被认为是太低效了。增加这种水解活性的裂解因子被证明对细胞是不可接受的。因此，确保回溯复合物的有效分辨率的机制仍然知之甚少。在这里，我提出了一个新的因子独立的机制，以解决回溯复合物，这将解释他们如何能够有效地解决在转录过程中。该提议基于以下假设（由初步结果支持）：i）回溯复合物的解析发生在模板DNA上的特定位点，在该位点转录物切割反应高度增加; ii）转录物本身有助于回溯复合物中的切割，从而重新激活它们。我们将对这些假说进行验证，并进一步探讨回溯和拯救机制，这一提议的研究也将有助于加深对转录延伸复合物结构和性质的理解，并有助于阐明转录暂停和终止的机制。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Stepwise mechanism for transcription fidelity.

DOI：
10.1186/1741-7007-8-54
发表时间：
2010-05-07
期刊：
BMC biology
影响因子：
5.4
作者：
Yuzenkova Y;Bochkareva A;Tadigotla VR;Roghanian M;Zorov S;Severinov K;Zenkin N
通讯作者：
Zenkin N

Controlled interplay between trigger loop and Gre factor in the RNA polymerase active centre.

DOI：
10.1093/nar/gkq1359
发表时间：
2011-05
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Roghanian M;Yuzenkova Y;Zenkin N
通讯作者：
Zenkin N

Factor-independent transcription pausing caused by recognition of the RNA-DNA hybrid sequence.

DOI：
10.1038/emboj.2011.432
发表时间：
2012-02-01
期刊：
EMBO JOURNAL
影响因子：
11.4
作者：
Bochkareva, Aleksandra;Yuzenkova, Yulia;Tadigotla, Vasisht R.;Zenkin, Nikolay
通讯作者：
Zenkin, Nikolay

Tagetitoxin inhibits transcription by stabilizing pre-translocated state of the elongation complex.