The mechanism for RNA recognition by ANTAR regulators of gene expression.
The mechanism for RNA recognition by ANTAR regulators of gene expression.
复制标题
DOI：
10.1371/journal.pgen.1002666
复制
发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Winkler WC
中科院分区：
文献类型：
--
作者：
Ramesh A;DebRoy S;Goodson JR;Fox KA;Faz H;Garsin DA;Winkler WC
ANTAR蛋白是广泛存在的细菌调节蛋白，其具有RNA结合输出结构域并利用抗终止作用在起始后水平控制基因表达。一种ANTAR蛋白，EutV，调节粪肠球菌中的乙醇胺利用基因（eut）。使用这个系统，我们提出了遗传和生化证据的一般机制的antitermination所使用的ANTAR，包括细节的antiterminator结构。新的antiterminator结构由两个小发夹高度保守的终端环残基，这两个功能是成功的antitermination必不可少的。ANTAR蛋白二聚化并与其底物RNA结合以响应信号诱导的磷酸化。此外，生物信息学搜索使用这种保守的antiterminator基序确定了许多新的ANTAR靶RNA在不同的细菌物种，一些包含复杂的调节子。尽管发现它们的物种无关，但大多数ANTAR相关基因在主题上与氮管理相关。这些数据表明，通过ANTAR抗终止作用进行基因调控的中心原则在自然界中广泛存在，以特异性地控制氮代谢。在细菌中，双组分调节系统包括微生物如何响应其环境变化的主要机制。这些信号转导系统依赖于两种保守蛋白质（组氨酸激酶和反应调节剂）之间的磷酸转移来传播信号并影响细胞生物学。在许多系统中，反应调节剂的磷酸化已被证明可以控制DNA结合活性、蛋白质-蛋白质相互作用或酶活性。然而，在这项研究中，我们发现了一个一般的RNA底物的一个大家庭的推定RNA结合反应调节蛋白称为ANTAR蛋白。通过识别这种RNA识别元件的一般结构，我们的生物信息学搜索能够在细菌中发现更多这些RNA基序的例子。事实上，我们的数据共同揭示了ANTAR蛋白和本研究中鉴定的RNA基序之间的调节关系在遗传多样性细菌中广泛存在，用于控制许多氮代谢基因。
ANTAR proteins are widespread bacterial regulatory proteins that have RNA–binding output domains and utilize antitermination to control gene expression at the post-initiation level. An ANTAR protein, EutV, regulates the ethanolamine-utilization genes (eut) in Enterococcus faecalis. Using this system, we present genetic and biochemical evidence of a general mechanism of antitermination used by ANTARs, including details of the antiterminator structure. The novel antiterminator structure consists of two small hairpins with highly conserved terminal loop residues, both features being essential for successful antitermination. The ANTAR protein dimerizes and associates with its substrate RNA in response to signal-induced phosphorylation. Furthermore, bioinformatic searches using this conserved antiterminator motif identified many new ANTAR target RNAs in phylogenetically diverse bacterial species, some comprising complex regulons. Despite the unrelatedness of the species in which they are found, the majority of the ANTAR–associated genes are thematically related to nitrogen management. These data suggest that the central tenets for gene regulation by ANTAR antitermination occur widely in nature to specifically control nitrogen metabolism. In bacteria, two-component regulatory systems comprise the primary mechanisms for how microorganisms respond to changes in their environment. These signal transduction systems rely upon phosphotransfer between two conserved proteins, a histidine kinase and a response regulator, to propagate the signal and affect cellular biology. Phosphorylation of the response regulator has been shown in many systems to control DNA–binding activity, protein–protein interactions, or enzymatic activity. However, in this study, we discover a general RNA substrate for a large family of putative RNA–binding response regulator proteins called ANTAR proteins. By identifying the general architecture of this RNA recognition element, our bioinformatic searches were then able to discover many more examples of these RNA motifs in bacteria. Indeed, our data together revealed that the regulatory relationship between ANTAR proteins and the RNA motif identified in this study is widespread among phylogenetically diverse bacteria for control of numerous nitrogen metabolism genes.
登录
查看更多内容
影响因子：
3.2
作者：
Baker, Kris Ann;Perego, Marta
通讯作者：
Perego, Marta
影响因子：
4.8
作者：
Norman, RA;Poh, CL;Drew, RE
通讯作者：
Drew, RE
影响因子：
14.9
作者：
Griffiths-Jones, S;Bateman, A;Eddy, SR
通讯作者：
Eddy, SR
影响因子：
5.7
作者：
Morth, JP;Feng, V;Tucker, PA
通讯作者：
Tucker, PA
DOI：
10.1073/pnas.89.21.10410
发表时间：
1992-11-01
影响因子：
11.1
作者：
AYMERICH, S;STEINMETZ, M
通讯作者：
STEINMETZ, M