Chen Ziying, Yang Yaomei, Chen Xiaomin, Bei Cheng, Gao Qian, Chao Yanjie, Wang Chuan
Key Laboratory of Medical Molecular Virology (Ministry of Education / National Health Commission / Chinese Academy of Medical Sciences), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200033, China.
Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.
Proc Natl Acad Sci U S A. 2025 Jan 14;122(2):e2414563122. doi: 10.1073/pnas.2414563122. Epub 2025 Jan 10.
Sialic acids derived from colonic mucin glycans are crucial nutrients for enteric bacterial pathogens like . The uptake and utilization of sialic acid in depend on coordinated regulons, each activated by specific metabolites at the transcriptional level. However, the mechanisms enabling crosstalk among these regulatory circuits to synchronize gene expression remain poorly understood. Here, we identify ManS, a small noncoding RNA derived from the 3' UTR of mRNA transcribed from a -specific genetic locus, as an important posttranscriptional regulator coordinating sialic acid metabolism regulons. ManS is primarily processed by RNase III and, along with its parental transcripts, is specifically activated by N-acetylmannosamine (ManNAc), the initial degradation product of sialic acid. We found that the imperfect stem-loop structure at the 5' end of ManS allows RNase III to cleave in a noncanonical manner, generating two functional types of ManS with the assistance of RNase E and other RNases: short isoforms with a single seed region that regulate the uptake of N-acetylglucosamine, an essential intermediate in sialic acid metabolism; and long isoforms with an additional seed region that regulate multiple genes involved in central and secondary metabolism. This sophisticated regulation by ManS significantly impacts ManNAc metabolism and 's competitive behavior during infection. Our findings highlight the role of sRNA in coordinating transcriptional circuits and advance our understanding of RNase III-mediated processing of 3' UTR-derived sRNAs, underscoring the important role of ManNAc in adaptation within host environments.
源自结肠粘蛋白聚糖的唾液酸是诸如肠道细菌病原体的关键营养素。[具体病原体名称未给出]中唾液酸的摄取和利用取决于协调的调控子，每个调控子在转录水平上由特定代谢物激活。然而，使这些调控回路之间产生串扰以同步基因表达的机制仍知之甚少。在这里，我们鉴定出ManS，一种源自特定基因位点转录的[具体基因名称未给出]mRNA 3'UTR的小非编码RNA，作为协调唾液酸代谢调控子的重要转录后调节因子。ManS主要由RNase III加工，并且与其亲本转录本一起，被唾液酸的初始降解产物N-乙酰甘露糖胺（ManNAc）特异性激活。我们发现ManS 5'端的不完全茎环结构允许RNase III以非规范方式切割，在RNase E和其他核糖核酸酶的协助下产生两种功能类型的ManS：具有单个种子区域的短异构体，其调节N-乙酰葡糖胺的摄取，N-乙酰葡糖胺是唾液酸代谢中的必需中间体；以及具有额外种子区域的长异构体，其调节参与中心代谢和次生代谢的多个基因。ManS的这种复杂调节显著影响ManNAc代谢以及[具体病原体名称未给出]在感染期间的竞争行为。我们的发现突出了sRNA在协调转录回路中的作用，并推进了我们对RNase III介导的3'UTR衍生sRNA加工的理解，强调了ManNAc在[具体病原体名称未给出]适应宿主环境中的重要作用。
