Escherichia coli SymE is a DNA-binding protein that can condense the nucleoid.
Escherichia coli SymE is a DNA-binding protein that can condense the nucleoid.
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DOI：
10.1111/mmi.14877
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发表时间：
2022-04
影响因子：
3.6
通讯作者：
Laub, Michael T.
中科院分区：
文献类型：
--
作者：
Thompson, Mary K.;Nocedal, Isabel;Culviner, Peter H.;Zhang, Tong;Gozzi, Kevin R.;Laub, Michael T.
I 型毒素-抗毒素 (TA) 系统通常由嵌入内膜的蛋白质毒素和 RNA 抗毒素组成，其中蛋白质毒素嵌入内膜中，可以寡聚并形成改变膜通透性的孔，而 RNA 抗毒素则直接与毒素 mRNA 相互作用以抑制其翻译。在大肠杆菌中，symE/symR 被注释为具有非规范毒素的 I 型 TA 系统。 SymE 最初被认为是一种内切核糖核酸酶，但预测其与 DNA 结合蛋白的结构相似。为了更好地了解 SymE 功能，我们使用 RNA-seq 来检查异位产生 SymE 的细胞。尽管 SymE 驱动基因表达发生重大变化，但我们没有发现核糖核酸内切活性的有力证据。相反，我们的生化和细胞生物学研究表明 SymE 结合 DNA。我们证明，symE 过度表达的毒性可能源于其驱动严重核苷缩合的能力，这会破坏 DNA 和 RNA 合成并导致 DNA 损伤，类似于过度产生核苷相关蛋白 H-NS 的影响。总的来说，我们的结果表明 SymE 代表了一类新的核相关蛋白，广泛分布于细菌中。来自大肠杆菌的保守蛋白SymE最初被认为是切割RNA的I型毒素-抗毒素系统的毒素。然而，我们的生化和细胞生物学研究表明，SymE 相反会结合 DNA，并且当过度表达时，会导致严重的类核凝聚。这种缩合与 H-NS 观察到的类似，会破坏大量 DNA 和 RNA 的合成，并产生双链断裂。我们认为 SymE 代表了一类新的核相关蛋白。
Type I toxin-antitoxin (TA) systems typically consist of a protein toxin that imbeds in the inner membrane where it can oligomerize and form pores that change membrane permeability, and an RNA antitoxin that interacts directly with toxin mRNA to inhibit its translation. In Escherichia coli, symE/symR is annotated as a type I TA system with a non-canonical toxin. SymE was initially suggested to be an endoribonuclease, but has predicted structural similarity to DNA binding proteins. To better understand SymE function, we used RNA-seq to examine cells ectopically producing it. Although SymE drives major changes in gene expression, we do not find strong evidence of endoribonucleolytic activity. Instead, our biochemical and cell biological studies indicate that SymE binds DNA. We demonstrate that the toxicity of symE overexpression likely stems from its ability to drive severe nucleoid condensation, which disrupts DNA and RNA synthesis and leads to DNA damage, similar to the effects of overproducing the nucleoid-associated protein H-NS. Collectively, our results suggest that SymE represents a new class of nucleoid-associated proteins that is widely distributed in bacteria. The conserved protein SymE from Escherichia coli was originally thought to be a toxin of a type I toxin-antitoxin system that cleaves RNA. However, our biochemical and cell biological studies indicate that SymE instead binds DNA and can, when overexpressed, drive severe nucleoid condensation. This condensation, similar to that observed with H-NS, disrupts bulk DNA and RNA synthesis, and produces double-strand breaks. We propose that SymE represents a new class of nucleoid-associated protein.
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