The conserved 3′ UTR-derived small RNA NarS mediates mRNA crossregulation during nitrate respiration
The conserved 3′ UTR-derived small RNA NarS mediates mRNA crossregulation during nitrate respiration
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DOI：
10.1093/nar/gkz1168
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发表时间：
2019-12
影响因子：
14.9
通讯作者：
Chuan Wang;Y. Chao;G. Matera;Q. Gao;J. Vogel
中科院分区：
文献类型：
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作者：
Chuan Wang;Y. Chao;G. Matera;Q. Gao;J. Vogel
摘要 来自 mRNA 3' UTR 的小非编码 RNA (sRNA) 似乎呈现出一个先前未被识别的细菌转录后控制层，其中 mRNA 独立于转录控制而影响彼此的表达。对大肠杆菌和肠沙门氏菌的研究表明，此类 sRNA 是 RNase E 介导的 mRNA 降解的天然产物，并与 Hfq 和 ProQ 等主要 RNA 结合蛋白 (RBP) 相关。如果是这样，那么一定有来自 mRNA 的额外 sRNA 仅在特定的生理条件下积累。我们通过表征代表硝酸盐转运蛋白 NarK 的 3'UTR 的候选 NarS 来测试这一预测，NarK 的基因在标准有氧生长期间是沉默的。我们发现 NarS 通过 Hfq 依赖的碱基配对来抑制亚硝酸盐转运蛋白 NirC 的合成，从而导致硝酸盐和亚硝酸盐转运蛋白基因的 mRNA 交叉调节。有趣的是，NarS 介导的抑制选择性地针对长 nirBDC-cysG 操纵子的 nirC 顺反子，我们将这一观察结果合理化为在富含硝酸盐的无氧呼吸过程中保护细菌细胞质免受过量亚硝酸盐毒性的机制。我们对来自非标准生长条件的 3'UTR sRNA 的成功功能分配支持了这样的观点：mRNA 交叉调节比目前认为的更为普遍。
Abstract Small noncoding RNAs (sRNAs) from mRNA 3′ UTRs seem to present a previously unrecognized layer of bacterial post-transcriptional control whereby mRNAs influence each other's expression, independently of transcriptional control. Studies in Escherichia coli and Salmonella enterica showed that such sRNAs are natural products of RNase E-mediated mRNA decay and associate with major RNA-binding proteins (RBPs) such as Hfq and ProQ. If so, there must be additional sRNAs from mRNAs that accumulate only under specific physiological conditions. We test this prediction by characterizing candidate NarS that represents the 3′ UTR of nitrate transporter NarK whose gene is silent during standard aerobic growth. We find that NarS acts by Hfq-dependent base pairing to repress the synthesis of the nitrite transporter, NirC, resulting in mRNA cross-regulation of nitrate and nitrite transporter genes. Interestingly, the NarS-mediated repression selectively targets the nirC cistron of the long nirBDC-cysG operon, an observation that we rationalize as a mechanism to protect the bacterial cytoplasm from excessive nitrite toxicity during anaerobic respiration with abundant nitrate. Our successful functional assignment of a 3′ UTR sRNA from a non-standard growth condition supports the notion that mRNA crossregulation is more pervasive than currently appreciated.