Targeted decay of a regulatory small RNA by an adaptor protein for RNase E and counteraction by an anti-adaptor RNA
Targeted decay of a regulatory small RNA by an adaptor protein for RNase E and counteraction by an anti-adaptor RNA
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DOI：
10.1101/gad.210112.112
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发表时间：
2013-03-01
影响因子：
10.5
通讯作者：
Goerke, Boris
中科院分区：
文献类型：
--
作者：
Goepel, Yvonne;Papenfort, Kai;Goerke, Boris
细菌小RNA（sRNA）已被公认为调节多种细胞过程，但它们本身是如何被调节的还不太清楚。最近，我们确定了一个调节回路，其中大肠杆菌的GlmY和GlmZ sRNA分层激活mRNA glmS，其编码葡萄糖胺-6-磷酸（GlcN 6P）合酶。虽然这两种sRNA高度相似，但只有GlmZ是一种直接激活剂，在蛋白Hfq的帮助下与glmS mRNA进行碱基配对。然而，GlmY不结合Hfq，并通过保护GlmZ免受RNA切割而间接激活glmS。这种复杂的调节反馈控制GlmS蛋白的水平，以响应其产物GlcN 6P，GlcN 6P是细胞壁生物合成中的关键代谢物。在这里，我们揭示了GlmZ的调节营业额的分子基础，确定RapZ（核糖核酸酶衔接蛋白sRNA GlmZ;以前YhbJ）作为一种新型的RNA结合蛋白，招募主要的核糖核酸内切酶RNase E GlmZ。这涉及RapZ与RNase E的催化结构域的直接相互作用。GlmY通过两种sRNA共有的二级结构结合RapZ，因此通过分子模拟作为RapZ的特异性诱饵。因此，类似于调节的蛋白水解，RapZ是调节小RNA的调节周转中的衔接子，而GlmY是反衔接子。
Bacterial small RNAs (sRNAs) are well established to regulate diverse cellular processes, but how they themselves are regulated is less understood. Recently, we identified a regulatory circuit wherein the GlmY and GlmZ sRNAs of Escherichia coli act hierarchically to activate mRNA glmS, which encodes glucosamine-6-phosphate (GlcN6P) synthase. Although the two sRNAs are highly similar, only GlmZ is a direct activator that base-pairs with the glmS mRNA, aided by protein Hfq. GlmY, however, does not bind Hfq and activates glmS indirectly by protecting GlmZ from RNA cleavage. This complex regulation feedback controls the levels of GlmS protein in response to its product, GlcN6P, a key metabolite in cell wall biosynthesis. Here, we reveal the molecular basis for the regulated turnover of GlmZ, identifying RapZ (RNase adaptor protein for sRNA GlmZ; formerly YhbJ) as a novel type of RNA-binding protein that recruits the major endoribonuclease RNase E to GlmZ. This involves direct interaction of RapZ with the catalytic domain of RNase E. GlmY binds RapZ through a secondary structure shared by both sRNAs and therefore acts by molecular mimicry as a specific decoy for RapZ. Thus, in analogy to regulated proteolysis, RapZ is an adaptor, and GlmY is an anti-adaptor in regulated turnover of a regulatory small RNA.