Transcriptional regulation of NAD metabolism in bacteria: genomic reconstruction of NiaR (YrxA) regulon.

Transcriptional regulation of NAD metabolism in bacteria: genomic reconstruction of NiaR (YrxA) regulon.
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DOI:
10.1093/nar/gkn046
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发表时间:
2008-04
影响因子:
14.9
通讯作者:
Osterman AL
Osterman AL
中科院分区:
生物学2区
文献类型:
--
作者:
Rodionov DA;Li X;Rodionova IA;Yang C;Sorci L;Dervyn E;Martynowski D;Zhang H;Gelfand MS;Osterman AL

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比较基因组学方法被用来重建转录调控的NAD生物合成的细菌含有枯草芽孢杆菌基因yrxA,一个先前确定的烟酸反应抑制NAD从头合成的直系同源物。YrxA家族的成员(在此重新命名为NiaR)在芽孢杆菌/梭菌属群和深分支的梭菌门和嗜热菌门谱系中广泛保守。我们分析了与NAD生物合成相关的基因上游区域,以识别候选的NiaR结合DNA基序并评估这些物种中的NiaR调节子含量。两种不同类型的候选NiaR结合位点的代表,厚壁菌门和Thermotogales的特征,通过电泳迁移率变动试验进行了验证。除了nadABC基因的转录控制,在一些物种中的NiaR调节子延伸到烟酸补救(pncAB基因),并包括未表征的膜蛋白可能参与烟酸运输。参与烟酸摄取的是由B编码的这些蛋白质之一(重新命名为NiaP)。枯草芽孢杆菌基因yceI,实验验证。除了细菌,NiaP家族的成员在多细胞真核生物中是保守的,包括人类,这表明NaiP可能参与这些生物体中的烟酸利用。总体而言,NiaR和NrtR调节子的分析(在随附的论文中描述)揭示了近一百种不同细菌中NAD代谢的转录调节机制。
A comparative genomic approach was used to reconstruct transcriptional regulation of NAD biosynthesis in bacteria containing orthologs of Bacillus subtilis gene yrxA, a previously identified niacin-responsive repressor of NAD de novo synthesis. Members of YrxA family (re-named here NiaR) are broadly conserved in the Bacillus/Clostridium group and in the deeply branching Fusobacteria and Thermotogales lineages. We analyzed upstream regions of genes associated with NAD biosynthesis to identify candidate NiaR-binding DNA motifs and assess the NiaR regulon content in these species. Representatives of the two distinct types of candidate NiaR-binding sites, characteristic of the Firmicutes and Thermotogales, were verified by an electrophoretic mobility shift assay. In addition to transcriptional control of the nadABC genes, the NiaR regulon in some species extends to niacin salvage (the pncAB genes) and includes uncharacterized membrane proteins possibly involved in niacin transport. The involvement in niacin uptake proposed for one of these proteins (re-named NiaP), encoded by the B. subtilis gene yceI, was experimentally verified. In addition to bacteria, members of the NiaP family are conserved in multicellular eukaryotes, including human, pointing to possible NaiP involvement in niacin utilization in these organisms. Overall, the analysis of the NiaR and NrtR regulons (described in the accompanying paper) revealed mechanisms of transcriptional regulation of NAD metabolism in nearly a hundred diverse bacteria.
Pfam:氏族、网络工具和服务。
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