RNase Y-mediated regulation of the streptococcal pyrogenic exotoxin B.

RNase Y-mediated regulation of the streptococcal pyrogenic exotoxin B.
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DOI:
10.1080/15476286.2018.1532253
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发表时间:
2018
期刊:
影响因子:
4.1
通讯作者:
Charpentier E
Charpentier E
中科院分区:
生物学3区
文献类型:
--
作者:
Broglia L;Materne S;Lécrivain AL;Hahnke K;Le Rhun A;Charpentier E

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核糖核酸酶Y(RNase Y)是革兰氏阳性菌毒力的重要调节因子。在人类致病菌化脓性链球菌中,主要分泌性毒力因子链球菌热原外毒素B(SpeB)的表达需要核糖核酸酶Y,但其调控机制尚不清楚。在这里,我们证明了SpeB mRNA的5‘非翻译区被包括RNase Y在内的几个RNase处理。特别是,我们发现了位于鸟苷(G)残基下游的两个RNase Y裂解位点。为了评估这个核苷酸是否是RNase Y在体内活性所必需的,我们对其进行了突变,并证明了这个G残基的存在对于RNaseY处理SpeB mRNA 5‘UTR是必不可少的。虽然RNaseY直接靶向和处理SpeB,但我们表明RNaseY介导的SpeB表达的调节主要发生在转录水平,而不依赖于SpeB mRNA 5’UTR中的处理。综上所述,我们首次证明了RNaseY对mRNA靶标的处理需要G的存在。我们还对SpeB5‘UTR和RNaseY在SpeB调控中的作用提供了新的见解。
Endoribonuclease Y (RNase Y) is a crucial regulator of virulence in Gram-positive bacteria. In the human pathogen Streptococcus pyogenes, RNase Y is required for the expression of the major secreted virulence factor streptococcal pyrogenic exotoxin B (SpeB), but the mechanism involved in this regulation remains elusive. Here, we demonstrate that the 5′ untranslated region of speB mRNA is processed by several RNases including RNase Y. In particular, we identify two RNase Y cleavage sites located downstream of a guanosine (G) residue. To assess whether this nucleotide is required for RNase Y activity in vivo, we mutated it and demonstrate that the presence of this G residue is essential for the processing of the speB mRNA 5′ UTR by RNase Y. Although RNase Y directly targets and processes speB, we show that RNase Y-mediated regulation of speB expression occurs primarily at the transcriptional level and independently of the processing in the speB mRNA 5′ UTR. To conclude, we demonstrate for the first time that RNase Y processing of an mRNA target requires the presence of a G. We also provide new insights on the speB 5′ UTR and on the role of RNase Y in speB regulation.
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