scholarly journals Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Guo-dong Zhu ◽  
Jing Yu ◽  
Zheng-yu Sun ◽  
Yan Chen ◽  
Hong-mei Zheng ◽  
...  
Keyword(s):  
Cold Shock ◽  
Mrna Level ◽  
Critical Role ◽  
Inflammatory Signaling ◽  
Heat Stable ◽  
Genome Wide ◽  
Attractive Therapeutic Target ◽  
Heat Stable Protein ◽  
Signaling Activation ◽  
Shock Proteins

AbstractGlioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening. This is a protein with a cold-shock domain (CSD)-containing that is highly similar to cold-shock proteins. CARHSP1 mRNA level was upregulated in irradiation-resistant GBM cells and knockdown of CARHSP1 sensitized GBM cells to radiotherapy. The high expression of CARHSP1 upon radiation might mediate radioresistance by activating the inflammatory signaling pathway. More importantly, patients with high levels of CARHSP1 had poorer survival when treated with radiotherapy. Collectively, our findings suggested that targeting the CARHSP1/TNF-α inflammatory signaling activation induced by radiotherapy might directly affect radioresistance and present an attractive therapeutic target for GBM, particularly for patients with high levels of CARHSP1.

scholarly journals Selective mRNA Degradation by Polynucleotide Phosphorylase in Cold Shock Adaptation in Escherichia coli

2001 ◽  
Vol 183 (9) ◽  
pp. 2808-2816 ◽  
Author(s):  
Kunitoshi Yamanaka ◽  
Masayori Inouye
Keyword(s):  
Escherichia Coli ◽  
Cell Growth ◽  
Cold Shock ◽  
Critical Role ◽  
Rna Helicase ◽  
Cold Shock Protein ◽  
Polynucleotide Phosphorylase ◽  
Selective Degradation ◽  
High Level ◽  
Shock Proteins

ABSTRACT Upon cold shock, Escherichia coli cell growth transiently stops. During this acclimation phase, specific cold shock proteins (CSPs) are highly induced. At the end of the acclimation phase, their synthesis is reduced to new basal levels, while the non-cold shock protein synthesis is resumed, resulting in cell growth reinitiation. Here, we report that polynucleotide phosphorylase (PNPase) is required to repress CSP production at the end of the acclimation phase. A pnp mutant, upon cold shock, maintained a high level of CSPs even after 24 h. PNPase was found to be essential for selective degradation of CSP mRNAs at 15°C. In a poly(A) polymerase mutant and a CsdA RNA helicase mutant, CSP expression upon cold shock was significantly prolonged, indicating that PNPase in concert with poly(A) polymerase and CsdA RNA helicase plays a critical role in cold shock adaptation.

Genome-wide identification and characterization of transcripts translationally regulated by bacterial lipopolysaccharide in macrophage-like J774.1 cells

2008 ◽  
Vol 33 (1) ◽  
pp. 121-132 ◽  
Author(s):  
Hiroshi Kitamura ◽  
Masatoshi Ito ◽  
Tomoko Yuasa ◽  
Chisato Kikuguchi ◽  
Atsushi Hijikata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Respiratory Chain ◽  
Mrna Level ◽  
Critical Role ◽  
Mitochondrial Respiratory Chain ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Genome Wide ◽  
A Genome ◽  
Mitochondrial Respiratory

Although Escherichia coli LPS is known to elicit various proinflammatory responses in macrophages, its effect on the translational states of transcripts has not yet been explored on a genome-wide scale. To address this, we investigated the mRNA profiles in polysomal and free messenger ribonucleoprotein particle (mRNP) fractions of mouse macrophage-like J774.1 cells, using Affymetrix Mouse Genome 430 2.0 GeneChips. Comparison of the mRNA profiles in total cellular, polysomal, and free mRNP fractions enabled us to identify transcripts that were modulated at the translational level by LPS: among 19,791 transcripts, 115 and 418 were up- and downregulated at 1, 2, or 4 h after LPS stimulation (100 ng/ml) in a translation-dependent manner. Interestingly, gene ontology-based analysis suggested that translation-dependent downregulated genes frequently include those encoding proteins in the mitochondrial respiratory chain. In fact, the mRNA levels of some transcripts for complexes I, IV, and V in the mitochondrial respiratory chain were translationally downregulated, eventually contributing to the decline of their protein levels. Moreover, the amount of metabolically labeled cytochrome oxidase subunit Va in complex IV was decreased without any change of its mRNA level in total cellular fraction after LPS stimulation. Consistently, the total amounts and activities of complexes I and IV were attenuated by LPS stimulation, and the attenuation was independent of nitric oxide. These results demonstrated that translational suppression may play a critical role in the LPS-mediated attenuation of mitochondrial oxidative phosphorylation in a nitric oxide-independent manner in J774.1 cells.

Microbial Cold Shock Proteins: Overview of their Function and Mechanism of Action

2021 ◽  
Vol 28 ◽  
Author(s):  
Yonghong Zhang ◽  
Changjie Bao ◽  
Lijun Shen ◽  
Chunjie Tian ◽  
Xueli Zang ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Molecular Chaperones ◽  
Low Temperatures ◽  
Cold Shock ◽  
Critical Role ◽  
Linear Chain ◽  
Cold Shock Proteins ◽  
Slowing Down ◽  
Wide Range ◽  
Shock Proteins

: The organism responds to a decrease in temperature by producing a series of cold shock proteins (CSPs). These proteins play a critical role in growing and functioning characteristic at low temperatures. CSPs have been discovered in a wide range of organisms and show enormous diversity; their mechanisms of action are also complicated. Transcription and translation in microorganisms typically occur via a single linear chain, but upon exposure to low temperatures, RNA forms a complex secondary structure that prevents ribosomes from binding to it, slowing down translation. CSPs bind to mRNA as RNA molecular chaperones to keep the mRNA secondary structure in a single-stranded linear conformation, allowing successful translation at low temperatures.

scholarly journals Genome-wide identification of cyclin-dependent kinase (CDK) genes affecting adipocyte differentiation in cattle

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cuili Pan ◽  
Zhaoxiong Lei ◽  
Shuzhe Wang ◽  
Xingping Wang ◽  
Dawei Wei ◽  
...  
Keyword(s):  
Gene Family ◽  
Expression Analysis ◽  
Adipocyte Differentiation ◽  
Bos Taurus ◽  
Adipogenic Differentiation ◽  
Critical Role ◽  
Bos Indicus ◽  
Specific Expression ◽  
Genome Wide ◽  
A Genome

Abstract Background Cyclin-dependent kinases (CDKs) are protein kinases regulating important cellular processes such as cell cycle and transcription. Many CDK genes also play a critical role during adipogenic differentiation, but the role of CDK gene family in regulating bovine adipocyte differentiation has not been studied. Therefore, the present study aims to characterize the CDK gene family in bovine and study their expression pattern during adipocyte differentiation. Results We performed a genome-wide analysis and identified a number of CDK genes in several bovine species. The CDK genes were classified into 8 subfamilies through phylogenetic analysis. We found that 25 bovine CDK genes were distributed in 16 different chromosomes. Collinearity analysis revealed that the CDK gene family in Bos taurus is homologous with Bos indicus, Hybrid-Bos taurus, Hybrid Bos indicus, Bos grunniens and Bubalus bubalis. Several CDK genes had higher expression levels in preadipocytes than in differentiated adipocytes, as shown by RNA-seq analysis and qPCR, suggesting a role in the growth of emerging lipid droplets. Conclusion In this research, 185 CDK genes were identified and grouped into eight distinct clades in Bovidae, showing extensively homology. Global expression analysis of different bovine tissues and specific expression analysis during adipocytes differentiation revealed CDK4, CDK7, CDK8, CDK9 and CDK14 may be involved in bovine adipocyte differentiation. The results provide a basis for further study to determine the roles of CDK gene family in regulating adipocyte differentiation, which is beneficial for beef quality improvement.

scholarly journals Listeria monocytogenes Cold Shock Proteins: Small Proteins with A Huge Impact

2021 ◽  
Vol 9 (5) ◽  
pp. 1061
Author(s):  
Francis Muchaamba ◽  
Roger Stephan ◽  
Taurai Tasara
Keyword(s):  
Listeria Monocytogenes ◽  
Stress Tolerance ◽  
Cold Shock ◽  
Current Data ◽  
Health Concern ◽  
Stress Exposure ◽  
Cold Shock Proteins ◽  
Cell Functions ◽  
Small Proteins ◽  
Shock Proteins

Listeria monocytogenes has evolved an extensive array of mechanisms for coping with stress and adapting to changing environmental conditions, ensuring its virulence phenotype expression. For this reason, L. monocytogenes has been identified as a significant food safety and public health concern. Among these adaptation systems are cold shock proteins (Csps), which facilitate rapid response to stress exposure. L. monocytogenes has three highly conserved csp genes, namely, cspA, cspB, and cspD. Using a series of csp deletion mutants, it has been shown that L. monocytogenes Csps are important for biofilm formation, motility, cold, osmotic, desiccation, and oxidative stress tolerance. Moreover, they are involved in overall virulence by impacting the expression of virulence-associated phenotypes, such as hemolysis and cell invasion. It is postulated that during stress exposure, Csps function to counteract harmful effects of stress, thereby preserving cell functions, such as DNA replication, transcription and translation, ensuring survival and growth of the cell. Interestingly, it seems that Csps might suppress tolerance to some stresses as their removal resulted in increased tolerance to stresses, such as desiccation for some strains. Differences in csp roles among strains from different genetic backgrounds are apparent for desiccation tolerance and biofilm production. Additionally, hierarchical trends for the different Csps and functional redundancies were observed on their influences on stress tolerance and virulence. Overall current data suggest that Csps have a wider role in bacteria physiology than previously assumed.

scholarly journals Histatin-1 Attenuates LPS-Induced Inflammatory Signaling in RAW264.7 Macrophages

2021 ◽  
Vol 22 (15) ◽  
pp. 7856
Author(s):  
Sang Min Lee ◽  
Kyung-No Son ◽  
Dhara Shah ◽  
Marwan Ali ◽  
Arun Balasubramaniam ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Mapk Signaling ◽  
Response To Treatment ◽  
No Production ◽  
Inflammatory Signaling ◽  
Raw264.7 Macrophages ◽  
Inflammatory Mediator Production

Macrophages play a critical role in the inflammatory response to environmental triggers, such as lipopolysaccharide (LPS). Inflammatory signaling through macrophages and the innate immune system are increasingly recognized as important contributors to multiple acute and chronic disease processes. Nitric oxide (NO) is a free radical that plays an important role in immune and inflammatory responses as an important intercellular messenger. In addition, NO has an important role in inflammatory responses in mucosal environments such as the ocular surface. Histatin peptides are well-established antimicrobial and wound healing agents. These peptides are important in multiple biological systems, playing roles in responses to the environment and immunomodulation. Given the importance of macrophages in responses to environmental triggers and pathogens, we investigated the effect of histatin-1 (Hst1) on LPS-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 (RAW) macrophages. LPS-induced inflammatory signaling, NO production and cytokine production in macrophages were tested in response to treatment with Hst1. Hst1 application significantly reduced LPS-induced NO production, inflammatory cytokine production, and inflammatory signaling through the JNK and NF-kB pathways in RAW cells. These results demonstrate that Hst1 can inhibit LPS-induced inflammatory mediator production and MAPK signaling pathways in macrophages.

scholarly journals RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures

2021 ◽  
Vol 49 (6) ◽  
pp. 3409-3426
Author(s):  
Arancha Catalan-Moreno ◽  
Marta Cela ◽  
Pilar Menendez-Gil ◽  
Naiara Irurzun ◽  
Carlos J Caballero ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rna Structure ◽  
Cold Shock ◽  
Mrna Translation ◽  
Site Directed Mutagenesis ◽  
Rna Structures ◽  
Double Stranded Rna ◽  
Ambient Temperatures ◽  
Shock Proteins ◽  
Rna Hairpin

Abstract Thermoregulation of virulence genes in bacterial pathogens is essential for environment-to-host transition. However, the mechanisms governing cold adaptation when outside the host remain poorly understood. Here, we found that the production of cold shock proteins CspB and CspC from Staphylococcus aureus is controlled by two paralogous RNA thermoswitches. Through in silico prediction, enzymatic probing and site-directed mutagenesis, we demonstrated that cspB and cspC 5′UTRs adopt alternative RNA structures that shift from one another upon temperature shifts. The open (O) conformation that facilitates mRNA translation is favoured at ambient temperatures (22°C). Conversely, the alternative locked (L) conformation, where the ribosome binding site (RBS) is sequestered in a double-stranded RNA structure, is folded at host-related temperatures (37°C). These structural rearrangements depend on a long RNA hairpin found in the O conformation that sequesters the anti-RBS sequence. Notably, the remaining S. aureus CSP, CspA, may interact with a UUUGUUU motif located in the loop of this long hairpin and favour the folding of the L conformation. This folding represses CspB and CspC production at 37°C. Simultaneous deletion of the cspB/cspC genes or their RNA thermoswitches significantly decreases S. aureus growth rate at ambient temperatures, highlighting the importance of CspB/CspC thermoregulation when S. aureus transitions from the host to the environment.

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