气候变化领域集成服务门户(CCPortal): An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium

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DOI	10.1073/pnas.2103579118
	An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium
	Fuchs M.; Lamm-Schmidt V.; Sulzer J.; Ponath F.; Jenniches L.; Kirk J.A.; Fagan R.P.; Barquist L.; Vogel J.; Faber F.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:25
英文摘要	The gram-positive human pathogen Clostridioides difficile has emerged as the leading cause of antibiotic-associated diarrhea. However, little is known about the bacterium’s transcriptome architecture and mechanisms of posttranscriptional control. Here, we have applied transcription start site and termination mapping to generate a single-nucleotide–resolution RNA map of C. difficile 5′ and 3′ untranslated regions, operon structures, and noncoding regulators, including 42 sRNAs. Our results indicate functionality of many conserved riboswitches and predict cis-regulatory RNA elements upstream of multidrug resistance (MDR)-type ATP-binding cassette (ABC) transporters and transcriptional regulators. Despite growing evidence for a role of Hfq in RNA-based gene regulation in C. difficile, the functions of Hfq-based posttranscriptional regulatory networks in gram-positive pathogens remain controversial. Using Hfq immunoprecipitation followed by sequencing of bound RNA species (RIP-seq), we identify a large cohort of transcripts bound by Hfq and show that absence of Hfq affects transcript stabilities and steady-state levels. We demonstrate sRNA expression during intestinal colonization by C. difficile and identify infection-related signals impacting its expression. As a proof of concept, we show that the utilization of the abundant intestinal metabolite ethanolamine is regulated by the Hfq-dependent sRNA CDIF630nc_085. Overall, our study lays the foundation for understanding clostridial riboregulation with implications for the infection process and provides evidence for a global role of Hfq in posttranscriptional regulation in a gram-positive bacterium. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Small RNA \| Hfq \| differential RNA-seq \| C. difficile \| transcript termination site
语种	英语
scopus关键词	ethanolamine; Hfq protein; multidrug resistance associated protein; RNA; RNA binding protein; unclassified drug; 3' untranslated region; 5' untranslated region; animal experiment; Article; bacterial colonization; Clostridioides difficile; controlled study; immunoprecipitation; mouse; nonhuman; operon; protein function; protein RNA binding; regulatory RNA sequence; riboswitch; RNA sequencing; RNA stability; steady state; transcription initiation site; transcription regulation; transcription termination
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238512
作者单位	Institute for Molecular Infection Biology, Faculty of Medicine, University of Würzburg, Würzburg, 97080, Germany; Helmholtz Institute for RNA-based Infection Research, Helmholtz Centre for Infection Research, Würzburg, 97080, Germany; Florey Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, United Kingdom; Faculty of Medicine, University of Würzburg, Würzburg, 97080, Germany
推荐引用方式 GB/T 7714	Fuchs M.,Lamm-Schmidt V.,Sulzer J.,et al. An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium[J],2021,118(25).
APA	Fuchs M..,Lamm-Schmidt V..,Sulzer J..,Ponath F..,Jenniches L..,...&Faber F..(2021).An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium.Proceedings of the National Academy of Sciences of the United States of America,118(25).
MLA	Fuchs M.,et al."An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium".Proceedings of the National Academy of Sciences of the United States of America 118.25(2021).