scholarly journals Hfq-assisted RsmA regulation is central to Pseudomonas aeruginosa biofilm polysaccharide PEL expression

2018 ◽  
Author(s):  
Yasuhiko Irie ◽  
Victoriia Murina ◽  
Vasili Hauryliuk ◽  
Victoria Shingler
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Transcription Factor ◽  
Family Member ◽  
Mrna Stability ◽  
Rna Binding ◽  
Transcriptional Regulator ◽  
Regulatory Elements ◽  
Polysaccharide Biosynthesis ◽  
Chaperone Protein

ABSTRACTExpression of biofilm-associated genes is controlled by multiple regulatory elements, allowing bacteria to appropriately switch between sessile and motile lifestyles. In Pseudomonas aeruginosa, the post-transcriptional regulator RsmA has been implicated in the control of various genes including those related to biofilms, but much of the evidence for these links is limited to transcriptomic and phenotypic studies. RsmA binds to target mRNAs to modulate translation by affecting ribosomal access and/or mRNA stability. Here we trace a global regulatory role of RsmA to the inhibition of Vfr – a transcription factor that controls a transcriptional regulator FleQ. FleQ directly controls biofilm-associated genes that encode the PEL polysaccharide biosynthesis machinery. Furthermore, we show that RsmA cannot bind vfr mRNA alone, but requires the RNA chaperone protein Hfq. This is the first example where a RsmA protein family member is demonstrated to require another protein for RNA binding.

scholarly journals Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hong Wang ◽  
Aiping Duan ◽  
Jing Zhang ◽  
Qi Wang ◽  
Yuexian Xing ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucocorticoid Receptor ◽  
Protective Effect ◽  
Histone Modification ◽  
Regulatory Networks ◽  
Target Gene ◽  
Regulatory Elements ◽  
Chromatin Interactions ◽  
Super Enhancer

AbstractElucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.

Key role of an ADP − ribose - dependent transcriptional regulator of NAD metabolism for fitness and virulence of Pseudomonas aeruginosa

2017 ◽  
Vol 307 (1) ◽  
pp. 83-94 ◽  
Author(s):  
Elza Okon ◽  
Sarah Dethlefsen ◽  
Anna Pelnikevich ◽  
Andrea van Barneveld ◽  
Antje Munder ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Transcriptional Regulator ◽  
Nad Metabolism

scholarly journals Drosophila Zic family member odd-paired is needed for adult post-ecdysis maturation

Open Biology ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 190245
Author(s):  
Eléanor Simon ◽  
Sergio Fernández de la Puebla ◽  
Isabel Guerrero
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Family Member ◽  
Ectopic Expression ◽  
Functional Conservation ◽  
The Central Nervous System ◽  
Behavioural Sequence

Specific neuropeptides regulate in arthropods the shedding of the old cuticle (ecdysis) followed by maturation of the new cuticle. In Drosophila melanogaster , the last ecdysis occurs at eclosion from the pupal case, with a post-eclosion behavioural sequence that leads to wing extension, cuticle stretching and tanning. These events are highly stereotyped and are controlled by a subset of crustacean cardioactive peptide (CCAP) neurons through the expression of the neuropeptide Bursicon (Burs). We have studied the role of the transcription factor Odd-paired (Opa) during the post-eclosion period. We report that opa is expressed in the CCAP neurons of the central nervous system during various steps of the ecdysis process and in peripheral CCAP neurons innerving the larval muscles involved in adult ecdysis. We show that its downregulation alters Burs expression in the CCAP neurons. Ectopic expression of Opa, or the vertebrate homologue Zic2 , in the CCAP neurons also affects Burs expression, indicating an evolutionary functional conservation. Finally, our results show that, independently of its role in Burs regulation, Opa prevents death of CCAP neurons during larval development.

scholarly journals Upregulation of RBM24 Exacerbates Bladder Cancer Progression by Formatting Runx1t1/TCF4/miR-625-5p Feedback Loop

2020 ◽  
Author(s):  
Yue-Wei Yin ◽  
Kai-Long Liu ◽  
Bao-Sai Lu ◽  
Wei Li ◽  
Ya-Lin Niu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transcription Factor ◽  
Cancer Progression ◽  
Mrna Stability ◽  
Feedback Loop ◽  
Rna Binding ◽  
Luciferase Assay ◽  
Proximity Ligation Assay ◽  
Binding Motif ◽  
Mrna Levels

Abstract Background: RNA-binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development through regulation of pre-mRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remains unclear.Methods: Cell viability was examined by colony forming and MTT assays. Real-time quantitative PCR (RT-qPCR) and western blot analysis were used to detect the protein and mRNA levels. Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) were used to determine the protein-protein interaction. Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and oligo pull-down assays were used to verify DNA/RNA–protein interactions. Luciferase assay analysis was used to detect effects on transcription factor activity.Results: In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Runx1t1 in turn promoted RBM24 expression by interacting with TCF4. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and depressing transcription of miR-625-5p, which directly targets and normally suppresses RBM24 expression. RBM24-regulated BC cells proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop.Conclusions: In summary, these results indicate that a RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop plays a key role in BC oncogenesis. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.

scholarly journals Conceptual Advances in Control of Inflammation by the RNA-Binding Protein Tristetraprolin

2021 ◽  
Vol 12 ◽  
Author(s):  
Pavel Kovarik ◽  
Annika Bestehorn ◽  
Jeanne Fesselet
Keyword(s):  
Immune Responses ◽  
Mrna Stability ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Degradation ◽  
Decay Rates ◽  
Mrna Destabilization

Regulated changes in mRNA stability are critical drivers of gene expression adaptations to immunological cues. mRNA stability is controlled mainly by RNA-binding proteins (RBPs) which can directly cleave mRNA but more often act as adaptors for the recruitment of the RNA-degradation machinery. One of the most prominent RBPs with regulatory roles in the immune system is tristetraprolin (TTP). TTP targets mainly inflammation-associated mRNAs for degradation and is indispensable for the resolution of inflammation as well as the maintenance of immune homeostasis. Recent advances in the transcriptome-wide knowledge of mRNA expression and decay rates together with TTP binding sites in the target mRNAs revealed important limitations in our understanding of molecular mechanisms of TTP action. Such orthogonal analyses lead to the discovery that TTP binding destabilizes some bound mRNAs but not others in the same cell. Moreover, comparisons of various immune cells indicated that an mRNA can be destabilized by TTP in one cell type while it remains stable in a different cell linage despite the presence of TTP. The action of TTP extends from mRNA destabilization to inhibition of translation in a subset of targets. This article will discuss these unexpected context-dependent functions and their implications for the regulation of immune responses. Attention will be also payed to new insights into the role of TTP in physiology and tissue homeostasis.

scholarly journals Transcription Factor FOXK1 Regulates the lncRNA NEAT1 to Promote Glioma Development Through Mediating KDM3A

2020 ◽  
Author(s):  
Feng Liu ◽  
Hao Wu ◽  
Guangyong Wu ◽  
Jun Long ◽  
Jin Dai ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Viability ◽  
Rna Binding ◽  
Luciferase Reporter ◽  
Normal Brain ◽  
Invasion And Migration ◽  
Gene Assay ◽  
And Migration ◽  
Lncrna Neat1

Abstract Background: Long noncoding RNAs are widely studied in glioma. However, the role of the lncRNA NEAT1 and KDM3A in glioma has not yet been reported. We aimed to reveal the role of these two lncRNAs in the development of glioma through this study.Methods: Samples from glioma patients and normal brain tissues were collected, and the expression of NEAT1 was detected by qRT-PCR. A dual-luciferase reporter gene assay, chromatin immunoprecipitation (ChIP), RNA-binding protein immunoprecipitation (RIP), and RNA pulldown experiments were used to identify the relationship between FOXK1, NEAT1, miR-128, and KDM3A. The CCK8 assay, Transwell assay and flow cytometry were used to detect cell viability, invasion and migration ability, and the cell cycle and apoptosis, respectively. Tumor formation experiments verified the effect of NEAT1 on gliomas in vivo.Results: FOXK1 and NEAT1 were significantly overexpressed in glioma tissues and cells, and NEAT1 was significantly related to WHO classification. FOXK1 bound the NEAT1 gene promoter region in glioma cells, and interference with FOXK1 inhibited NEAT1 expression. NEAT1 inhibited miR-128 expression by binding miR-128; significantly improved cell viability and invasion and migration capabilities; increased the expression of KDM3A and activated the Wnt signaling pathway. Interference with KDM3A reversed the above results. In addition, interference with NEAT1 decreased KDM3A expression and inhibited tumor growth.Conclusion: Interference with NEAT1 promoted the expression of miR-128, thereby suppressing the expression of KDM3A and inhibiting the occurrence and development of glioma, while the expression of NEAT1 was shown to be regulated by the upstream transcription factor FOXK1.

scholarly journals The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Anthony J Linares ◽  
Chia-Ho Lin ◽  
Andrey Damianov ◽  
Katrina L Adams ◽  
Bennett G Novitch ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Cytoskeletal Proteins ◽  
Control Programs ◽  
Neuronal Progenitor ◽  
Neuronal Genes

The RNA-binding proteins PTBP1 and PTBP2 control programs of alternative splicing during neuronal development. PTBP2 was found to maintain embryonic splicing patterns of many synaptic and cytoskeletal proteins during differentiation of neuronal progenitor cells (NPCs) into early neurons. However, the role of the earlier PTBP1 program in embryonic stem cells (ESCs) and NPCs was not clear. We show that PTBP1 controls a program of neuronal gene expression that includes the transcription factor Pbx1. We identify exons specifically regulated by PTBP1 and not PTBP2 as mouse ESCs differentiate into NPCs. We find that PTBP1 represses Pbx1 exon 7 and the expression of the neuronal Pbx1a isoform in ESCs. Using CRISPR-Cas9 to delete regulatory elements for exon 7, we induce Pbx1a expression in ESCs, finding that this activates transcription of neuronal genes. Thus, PTBP1 controls the activity of Pbx1 to suppress its neuronal transcriptional program prior to induction of NPC development.

scholarly journals Genetic Analysis of the AdnA Regulon in Pseudomonas fluorescens: Nonessential Role of Flagella in Adhesion to Sand and Biofilm Formation

2003 ◽  
Vol 185 (2) ◽  
pp. 453-460 ◽  
Author(s):  
Eduardo A. Robleto ◽  
Inmaculada López-Hernández ◽  
Mark W. Silby ◽  
Stuart B. Levy
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Transcription Factor ◽  
Pseudomonas Fluorescens ◽  
Biofilm Formation ◽  
Deletion Mutant ◽  
Open Reading Frames ◽  
Cell Processes ◽  
Reading Frames ◽  
Insertion Mutants

ABSTRACT AdnA is a transcription factor in Pseudomonas fluorescens that affects flagellar synthesis, biofilm formation, and sand adhesion. To identify the AdnA regulon, we used a promoterless Tn5-lacZ element to study the phenotypes of insertion mutants in the presence and absence of AdnA. Of 12,000 insertions, we identified seven different putative open reading frames (ORFs) activated by AdnA (named aba for activated by AdnA). aba120 and aba177 showed homology to flgC and flgI, components of the basal body of the flagella in Pseudomonas aeruginosa. Two other insertions, aba18 and aba51, disrupted genes affecting chemotaxis. The mutant loci aba160 (possibly affecting lipopolysaccharide synthesis) and aba175 (unknown function) led to loss of flagella. The mutant bearing aba203 became motile when complemented with adnA, but the mutated gene showed no similarity to known genes. Curiously, aba18, aba51, aba160, and aba203 mutants formed biofilms even in the absence of AdnA, suppressing the phenotype of the adnA deletion mutant. The combined findings suggest that flagella are nonessential for sand attachment or biofilm formation. Sequence and promoter analyses indicate that AdnA affects at least 23 ORFs either directly or by polar effects. These results support the concept that AdnA regulates cell processes other than those directly related to flagellar synthesis and define a broader cadre of genes in P. fluorescens than that described so far for its homolog, FleQ, in P. aeruginosa.

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