Faculty Opinions recommendation of A qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics.

Author(s):  
Kathleen Hall
Cell ◽  
2015 ◽  
Vol 160 (1-2) ◽  
pp. 228-240 ◽  
Author(s):  
Lihui Feng ◽  
Steven T. Rutherford ◽  
Kai Papenfort ◽  
John D. Bagert ◽  
Julia C. van Kessel ◽  
...  

Author(s):  
Donglan Huang ◽  
Ke Zhang ◽  
Wenying Zheng ◽  
Ruixin Zhang ◽  
Jiale Chen ◽  
...  

Abstract Background Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a few lncRNAs have been characterized functionally. In this study, we aimed to identify novel lncRNAs involved in the progression of gastric carcinoma (GC) and explore their regulatory mechanisms and clinical significance in GC. Methods A lncRNA expression microarray was used to identify differential lncRNA expression profiles between paired GCs and adjacent normal mucosal tissues. Using the above method, the lncRNA SGO1-AS1 was selected for further study. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) were performed to detect SGO1-AS1 expression in GC tissues. Gain-of-function and loss-of-function analyses were performed to investigate the functions of SGO1-AS1 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Results SGO1-AS1 was downregulated in gastric carcinoma tissues compared to adjacent normal tissues, and its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. The functional experiments revealed that SGO1-AS1 inhibited GC cell invasion and metastasis in vitro and in vivo. Mechanistically, SGO1-AS1 facilitated TGFB1/2 mRNA decay by competitively binding the PTBP1 protein, resulting in reduced TGFβ production and, thus, preventing the epithelial-to-mesenchymal transition (EMT) and metastasis. In addition, in turn, TGFβ inhibited SGO1-AS1 transcription by inducing ZEB1. Thus, SGO1-AS1 and TGFβ form a double-negative feedback loop via ZEB1 to regulate the EMT and metastasis. Conclusions SGO1-AS1 functions as an endogenous inhibitor of the TGFβ pathway and suppresses gastric carcinoma metastasis, indicating a novel potential target for GC treatment.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (10) ◽  
pp. e1009888
Author(s):  
Bin Zhu ◽  
Linhong Li ◽  
Rui Wei ◽  
Pei Liang ◽  
Xiwu Gao

The evolution of resistance to insecticides is well known to be closely associated with the overexpression of detoxifying enzymes. Although the role of glutathione S-transferase (GST) genes in insecticide resistance has been widely reported, the underlying regulatory mechanisms are poorly understood. Here, one GST gene (GSTu1) and its antisense transcript (lnc-GSTu1-AS) were identified and cloned, and both of them were upregulated in several chlorantraniliprole-resistant Plutella xylostella populations. GSTu1 was confirmed to be involved in chlorantraniliprole resistance by direct degradation of this insecticide. Furthermore, we demonstrated that lnc-GSTu1-AS interacted with GSTu1 by forming an RNA duplex, which masked the binding site of miR-8525-5p at the GSTu1-3′UTR. In summary, we revealed that lnc-GSTu1-AS maintained the mRNA stability of GSTu1 by preventing its degradation that could have been induced by miR-8525-5p and thus increased the resistance of P. xylostella to chlorantraniliprole. Our findings reveal a new noncoding RNA-mediated pathway that regulates the expression of detoxifying enzymes in insecticide-resistant insects and offer opportunities for the further understanding of the mechanisms of insecticide and drug resistance.


2020 ◽  
Vol 61 (11) ◽  
pp. 1912-1918 ◽  
Author(s):  
Yongyao Xie ◽  
Letian Chen

Abstract The precise regulation of gibberellin (GA) metabolism and signaling is essential for plant development and environmental responses. Epigenetic regulatory mechanisms, such as histone modification, noncoding RNA-mediated regulation, chromatin remodeling and DNA methylation, are emerging as important means of fine-tuning gene expression. Recent studies have significantly improved our understanding of the relationships between epigenetic regulation and GA metabolism and signaling. Here, we summarize the molecular mechanisms by which epigenetic modifications affect GA metabolism and signaling pathways and provide new insight into an unfolding avenue of research related to the epigenetic regulation of GA pathways.


2015 ◽  
Vol 112 (44) ◽  
pp. E6038-E6047 ◽  
Author(s):  
Steven T. Rutherford ◽  
Julie S. Valastyan ◽  
Thibaud Taillefumier ◽  
Ned S. Wingreen ◽  
Bonnie L. Bassler

Five homologous noncoding small RNAs (sRNAs), called the Qrr1-5 sRNAs, function in the Vibrio harveyi quorum-sensing cascade to drive its operation. Qrr1-5 use four different regulatory mechanisms to control the expression of ∼20 mRNA targets. Little is known about the roles individual nucleotides play in mRNA target selection, in determining regulatory mechanism, or in defining Qrr potency and dynamics of target regulation. To identify the nucleotides vital for Qrr function, we developed a method we call RSort-Seq that combines saturating mutagenesis, fluorescence-activated cell sorting, high-throughput sequencing, and mutual information theory to explore the role that every nucleotide in Qrr4 plays in regulation of two mRNA targets, luxR and luxO. Companion biochemical assays allowed us to assign specific regulatory functions/underlying molecular mechanisms to each important base. This strategy yielded a regional map of nucleotides in Qrr4 vital for stability, Hfq interaction, stem-loop formation, and base pairing to both luxR and luxO, to luxR only, and to luxO only. In terms of nucleotides critical for sRNA function, the RSort-Seq analysis provided strikingly different results from those predicted by commonly used regulatory RNA-folding algorithms. This approach is applicable to any RNA–RNA interaction, including sRNAs in other bacteria and regulatory RNAs in higher organisms.


2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Amanda J. Kreuder ◽  
Brandon Ruddell ◽  
Kathy Mou ◽  
Alan Hassall ◽  
Qijing Zhang ◽  
...  

ABSTRACT Small noncoding RNAs (ncRNAs) are involved in many important physiological functions in pathogenic microorganisms. Previous studies have identified the presence of noncoding RNAs in the major zoonotic pathogen Campylobacter jejuni; however, few have been functionally characterized to date. CjNC110 is a conserved ncRNA in C. jejuni, located downstream of the luxS gene, which is responsible for the production of the quorum sensing molecule autoinducer-2 (AI-2). In this study, we utilized strand specific high-throughput RNAseq to identify potential targets or interactive partners of CjNC110 in a sheep abortion clone of C. jejuni. These data were then utilized to focus further phenotypic evaluation of the role of CjNC110 in motility, autoagglutination, quorum sensing, hydrogen peroxide sensitivity, and chicken colonization in C. jejuni. Inactivation of the CjNC110 ncRNA led to a statistically significant decrease in autoagglutination ability as well as increased motility and hydrogen peroxide sensitivity compared to the wild-type. Extracellular AI-2 detection was decreased in ΔCjNC110; however, intracellular AI-2 accumulation was significantly increased, suggesting a key role of CjNC110 in modulating the transport of AI-2. Notably, ΔCjNC110 also showed a decreased ability to colonize chickens. Complementation of CjNC110 restored all phenotypic changes back to wild-type levels. The collective results of the phenotypic and transcriptomic changes observed in our data provide valuable insights into the pathobiology of C. jejuni sheep abortion clone and strongly suggest that CjNC110 plays an important role in the regulation of energy taxis, flagellar glycosylation, cellular communication via quorum sensing, oxidative stress tolerance, and chicken colonization in this important zoonotic pathogen.


2007 ◽  
Vol 85 (4) ◽  
pp. 484-496 ◽  
Author(s):  
Oya Yazgan ◽  
Jocelyn E. Krebs

Genome sequencing and annotation has advanced our understanding of genome organization and gene structure but initially only allowed predictions of how many genes might be present. Mechanisms such as alternative splicing reveal that these predictions only scratch the surface of the true nature of the transcriptome. Several thousand expressed partial gene fragments have been cloned but were considered transcriptional noise or cloning artifacts. We now know that genomes are indeed expressed at much higher levels than was previously predicted, and much of the additional transcription maps to intergenic regions, intron sequences, and untranslated regions of mRNAs. These transcripts are expressed from either the sense or the antisense strand and can be confirmed by conventional techniques. In addition to the already established roles for small RNAs in gene regulation, large noncoding RNAs (ncRNAs) are also emerging as potent regulators of gene expression. In this review, we summarize several illustrative examples of gene regulatory mechanisms that involve large ncRNAs. We describe several distinct regulatory mechanisms that involve large ncRNAs, such as transcriptional interference and promoter inactivation, as well as indirect effects on transcription regulatory proteins and in genomic imprinting. These diverse functions for large ncRNAs are likely to be only the first of many novel regulatory mechanisms emerging from this growing field.


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