RNA editing in bacteria recodes multiple proteins and regulates an evolutionarily conserved toxin-antitoxin system.
RNA editing in bacteria recodes multiple proteins and regulates an evolutionarily conserved toxin-antitoxin system.
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DOI：
10.1101/gr.222760.117
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发表时间：
2017-10
期刊：
影响因子：
7
通讯作者：
Pilpel Y
中科院分区：
文献类型：
--
作者：
Bar-Yaacov D;Mordret E;Towers R;Biniashvili T;Soyris C;Schwartz S;Dahan O;Pilpel Y
腺苷(A)到肌苷(I)的RNA编辑在真核生物中广泛存在。然而，在原核生物中，A-to-I RNA编辑只在tRNA中发生，而在蛋白质编码基因中没有。通过比较大肠杆菌的DNA和RNA序列，我们首次表明A-to-I编辑也存在于原核生物的mRNAs中，并有可能影响翻译的蛋白质和细胞生理。我们发现了15个新的A-to-I编辑事件，其中12个发生在已知的蛋白质编码基因中，它们总是将酪氨酸(TAC)重新编码为半胱氨酸(TGC)密码子。此外，我们还确定tRNA特异的腺苷脱氨酶(TADA)是所有这些编辑位点的编辑酶，从而使其成为第一个同时修饰tRNAs和mRNAs的RNA编辑酶。有趣的是，几个编辑目标是自杀性毒素，属于进化上保守的毒素-抗毒素对。我们把重点放在hokB上，这是一种通过抑制生长而赋予抗生素耐受性的毒素，因为它展示了这种mRNA编辑的最高水平。我们确定了编辑过的和毒素中DNA硬编码半胱氨酸残基位置之间的相关突变模式，并证明了在另外两个细菌物种中，RNA编辑发生在hokB中。因此，不仅毒素在进化上是保守的，而且毒素内部的编辑本身也是保守的。最后，我们发现hokB中的RNA编辑随着细胞密度的增加而增加，并增强了其毒性。因此，我们的工作证明了细菌中RNA编辑的发生、调节和功能后果。
Adenosine (A) to inosine (I) RNA editing is widespread in eukaryotes. In prokaryotes, however, A-to-I RNA editing was only reported to occur in tRNAs but not in protein-coding genes. By comparing DNA and RNA sequences of Escherichia coli, we show for the first time that A-to-I editing occurs also in prokaryotic mRNAs and has the potential to affect the translated proteins and cell physiology. We found 15 novel A-to-I editing events, of which 12 occurred within known protein-coding genes where they always recode a tyrosine (TAC) into a cysteine (TGC) codon. Furthermore, we identified the tRNA-specific adenosine deaminase (tadA) as the editing enzyme of all these editing sites, thus making it the first identified RNA editing enzyme that modifies both tRNAs and mRNAs. Interestingly, several of the editing targets are self-killing toxins that belong to evolutionarily conserved toxin-antitoxin pairs. We focused on hokB, a toxin that confers antibiotic tolerance by growth inhibition, as it demonstrated the highest level of such mRNA editing. We identified a correlated mutation pattern between the edited and a DNA hard-coded Cys residue positions in the toxin and demonstrated that RNA editing occurs in hokB in two additional bacterial species. Thus, not only the toxin is evolutionarily conserved but also the editing itself within the toxin is. Finally, we found that RNA editing in hokB increases as a function of cell density and enhances its toxicity. Our work thus demonstrates the occurrence, regulation, and functional consequences of RNA editing in bacteria.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
9.8
作者：
Bar-Yaacov D;Frumkin I;Yashiro Y;Chujo T;Ishigami Y;Chemla Y;Blumberg A;Schlesinger O;Bieri P;Greber B;Ban N;Zarivach R;Alfonta L;Pilpel Y;Suzuki T;Mishmar D
通讯作者：
Mishmar D
影响因子：
48
作者：
Ramaswami, Gokul;Zhang, Rui;Piskol, Robert;Keegan, Liam P.;Deng, Patricia;O'Connell, Mary A.;Li, Jin Billy
通讯作者：
Li, Jin Billy
影响因子：
7
作者：
Liu H;Wang Q;He Y;Chen L;Hao C;Jiang C;Li Y;Dai Y;Kang Z;Xu JR
通讯作者：
Xu JR
影响因子：
3.6
作者：
Pedersen, K;Gerdes, K
通讯作者：
Gerdes, K