scholarly journals SAFA facilitates chromatin opening of immune genes through interacting with nascent antiviral RNAs

2021 ◽  
Author(s):  
Lili Cao ◽  
Yunfei Li ◽  
Yujie Luo ◽  
Xuefei Guo ◽  
Siji Li ◽  
...  
Keyword(s):  
Viral Infection ◽  
Matrix Protein ◽  
Rna Binding ◽  
Expression Patterns ◽  
Chromatin Accessibility ◽  
Specific Gene ◽  
Dependent Manner ◽  
Immune Genes ◽  
C Terminus ◽  
A Genome

Regulation of chromatin accessibility determines the transcription activities of genes, which endow the host with function specific gene expression patterns. It remains unclear how chromatin accessibility is specifically directed, particularly, during host defense against viral infection. We previously reported that the nuclear matrix protein SAFA surveils viral RNA and regulates antiviral immune genes expression. However, how SAFA regulates the expression and what determines the specificity of antiviral immune genes remains unknown. Here, we identified that the depletion of SAFA specifically decreased the chromatin accessibility, activation and expression of virus induced genes in a genome wide scale after VSV infection. SAFA exclusively bound with antiviral related RNAs, which mediated the specific opening of the according chromatin and robust transcription of these genes. Knockdown of these associated RNAs dampened the accessibility of corresponding genes in an extranuclear signaling pathway dependent manner. Moreover, VSV infection cleaved SAFA protein at the C terminus which deprived its RNA binding ability for immune evasion. Thus, our results demonstrated that SAFA and the interacting RNA products during viral infection collaborate and remodel chromatin accessibility to facilitate anti viral innate immune response.

scholarly journals Limit cycle dynamics can guide the evolution of gene regulatory networks towards point attractors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stuart P. Wilson ◽  
Sebastian S. James ◽  
Daniel J. Whiteley ◽  
Leah A. Krubitzer
Keyword(s):  
Gene Expression ◽  
Limit Cycles ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Specific Gene ◽  
Boolean Models ◽  
A Genome ◽  
Order Of Magnitude ◽  
Accelerate Evolution

AbstractDevelopmental dynamics in Boolean models of gene networks self-organize, either into point attractors (stable repeating patterns of gene expression) or limit cycles (stable repeating sequences of patterns), depending on the network interactions specified by a genome of evolvable bits. Genome specifications for dynamics that can map specific gene expression patterns in early development onto specific point attractor patterns in later development are essentially impossible to discover by chance mutation alone, even for small networks. We show that selection for approximate mappings, dynamically maintained in the states comprising limit cycles, can accelerate evolution by at least an order of magnitude. These results suggest that self-organizing dynamics that occur within lifetimes can, in principle, guide natural selection across lifetimes.

scholarly journals The TEA Transcription Factor Tec1 Confers Promoter-Specific Gene Regulation by Ste12-Dependent and -Independent Mechanisms

2010 ◽  
Vol 9 (4) ◽  
pp. 514-531 ◽  
Author(s):  
Barbara Heise ◽  
Julia van der Felden ◽  
Sandra Kern ◽  
Mario Malcher ◽  
Stefan Brückner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Target Genes ◽  
Specific Gene ◽  
Dependent Manner ◽  
A Genome ◽  
Regulated Gene Expression

ABSTRACT In Saccharomyces cerevisiae, the TEA transcription factor Tec1 is known to regulate target genes together with a second transcription factor, Ste12. Tec1-Ste12 complexes can activate transcription through Tec1 binding sites (TCSs), which can be further combined with Ste12 binding sites (PREs) for cooperative DNA binding. However, previous studies have hinted that Tec1 might regulate transcription also without Ste12. Here, we show that in vivo, physiological amounts of Tec1 are sufficient to stimulate TCS-mediated gene expression and transcription of the FLO11 gene in the absence of Ste12. In vitro, Tec1 is able to bind TCS elements with high affinity and specificity without Ste12. Furthermore, Tec1 contains a C-terminal transcriptional activation domain that confers Ste12-independent activation of TCS-regulated gene expression. On a genome-wide scale, we identified 302 Tec1 target genes that constitute two distinct classes. A first class of 254 genes is regulated by Tec1 in a Ste12-dependent manner and is enriched for genes that are bound by Tec1 and Ste12 in vivo. In contrast, a second class of 48 genes can be regulated by Tec1 independently of Ste12 and is enriched for genes that are bound by the stress transcription factors Yap6, Nrg1, Cin5, Skn7, Hsf1, and Msn4. Finally, we find that combinatorial control by Tec1-Ste12 complexes stabilizes Tec1 against degradation. Our study suggests that Tec1 is able to regulate TCS-mediated gene expression by Ste12-dependent and Ste12-independent mechanisms that enable promoter-specific transcriptional control.

scholarly journals The multi-functional reovirus σ3 protein is a virulence factor that suppresses stress granule formation and is associated with myocardial injury

2021 ◽  
Vol 17 (7) ◽  
pp. e1009494
Author(s):  
Yingying Guo ◽  
Meleana M. Hinchman ◽  
Mercedes Lewandrowski ◽  
Shaun T. Cross ◽  
Danica M. Sutherland ◽  
...  
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Post Infection ◽  
Rna Binding ◽  
Binding Capacity ◽  
Binding Activity ◽  
Dependent Manner ◽  
Viral Protein Synthesis ◽  
Granule Formation ◽  
Dsrna Binding

The mammalian orthoreovirus double-stranded (ds) RNA-binding protein σ3 is a multifunctional protein that promotes viral protein synthesis and facilitates viral entry and assembly. The dsRNA-binding capacity of σ3 correlates with its capacity to prevent dsRNA-mediated activation of protein kinase R (PKR). However, the effect of σ3 binding to dsRNA during viral infection is largely unknown. To identify functions of σ3 dsRNA-binding activity during reovirus infection, we engineered a panel of thirteen σ3 mutants and screened them for the capacity to bind dsRNA. Six mutants were defective in dsRNA binding, and mutations in these constructs cluster in a putative dsRNA-binding region on the surface of σ3. Two recombinant viruses expressing these σ3 dsRNA-binding mutants, K287T and R296T, display strikingly different phenotypes. In a cell-type dependent manner, K287T, but not R296T, replicates less efficiently than wild-type (WT) virus. In cells in which K287T virus demonstrates a replication deficit, PKR activation occurs and abundant stress granules (SGs) are formed at late times post-infection. In contrast, the R296T virus retains the capacity to suppress activation of PKR and does not mediate formation of SGs at late times post-infection. These findings indicate that σ3 inhibits PKR independently of its capacity to bind dsRNA. In infected mice, K287T produces lower viral titers in the spleen, liver, lungs, and heart relative to WT or R296T. Moreover, mice inoculated with WT or R296T viruses develop myocarditis, whereas those inoculated with K287T do not. Overall, our results indicate that σ3 functions to suppress PKR activation and subsequent SG formation during viral infection and that these functions correlate with virulence in mice.

scholarly journals Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/PEBP2(alpha)) dependent activation of tissue-specific gene transcription

2000 ◽  
Vol 113 (12) ◽  
pp. 2221-2231 ◽  
Author(s):  
A. Javed ◽  
B. Guo ◽  
S. Hiebert ◽  
J.Y. Choi ◽  
J. Green ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Transcription ◽  
Nuclear Matrix ◽  
Gene Activation ◽  
Multi Drug Resistance ◽  
Specific Gene ◽  
Dependent Manner ◽  
Subnuclear Localization ◽  
Rous Sarcoma ◽  
C Terminus

The Runt related transcription factors RUNX (AML/CBF(alpha)/PEBP2(alpha)) are key regulators of hematopoiesis and osteogenesis. Using co-transfection experiments with four natural promoters, including those of the osteocalcin (OC), multi drug resistance (MDR), Rous Sarcoma Virus long terminal repeat (LTR), and bone sialoprotein (BSP) genes, we show that each of these promoters responds differently to the forced expression of RUNX proteins. However, the three RUNX subtypes (i.e. AML1, AML2, and AML3) regulate each promoter in a similar manner. Although the OC promoter is activated in a C terminus dependent manner, the MDR, LTR and BSP promoters are repressed by three distinct mechanisms, either independent of or involving the AML C terminus, or requiring only the conserved C-terminal pentapeptide VWRPY. Using yeast two hybrid assays we find that the C terminus of AML1 interacts with a Groucho/TLE/R-esp repressor protein. Co-expression assays reveal that TLE proteins repress AML dependent activation of OC gene transcription. Western and northern blot analyses suggest that TLE expression is regulated reciprocally with the levels of OC gene expression during osteoblast differentiation. Digital immunofluorescence microscopy results show that TLE1 and TLE2 are both associated with the nuclear matrix, and that a significant subset of each colocalizes with AML transcription factors. This co-localization of TLE and AML proteins is lost upon removing the C terminus of AML family members. Our findings indicate that suppression of AML-dependent gene activation by TLE proteins involves functional interactions with the C terminus of AML at the nuclear matrix in situ. Our data are consistent with the concept that the C termini of AML proteins support activation or repression of cell-type specific genes depending on the regulatory organization of the target promoter and subnuclear localization.

scholarly journals A genome-wide transcriptional analysis of morphology determination inCandida albicans

2013 ◽  
Vol 24 (3) ◽  
pp. 246-260 ◽  
Author(s):  
Patricia L. Carlisle ◽  
David Kadosh
Keyword(s):  
Gene Expression ◽  
Fungal Infections ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Transcriptional Analysis ◽  
Specific Gene ◽  
Genome Wide ◽  
A Genome ◽  
Genetically Manipulated

Candida albicans, the most common cause of human fungal infections, undergoes a reversible morphological transition from yeast to pseudohyphal and hyphal filaments, which is required for virulence. For many years, the relationship among global gene expression patterns associated with determination of specific C. albicans morphologies has remained obscure. Using a strain that can be genetically manipulated to sequentially transition from yeast to pseudohyphae to hyphae in the absence of complex environmental cues and upstream signaling pathways, we demonstrate by whole-genome transcriptional profiling that genes associated with pseudohyphae represent a subset of those associated with hyphae and are generally expressed at lower levels. Our results also strongly suggest that in addition to dosage, extended duration of filament-specific gene expression is sufficient to drive the C. albicans yeast-pseudohyphal-hyphal transition. Finally, we describe the first transcriptional profile of the C. albicans reverse hyphal-pseudohyphal-yeast transition and demonstrate that this transition involves not only down-regulation of known hyphal-specific, genes but also differential expression of additional genes that have not previously been associated with the forward transition, including many involved in protein synthesis. These findings provide new insight into genome-wide expression patterns important for determining fungal morphology and suggest that in addition to similarities, there are also fundamental differences in global gene expression as pathogenic filamentous fungi undergo forward and reverse morphological transitions.

scholarly journals Transcriptome-IPMS analysis reveals a tissue-dependent miR156/SPL13 regulatory mechanism in alfalfa drought tolerance

2020 ◽  
Author(s):  
Biruk A Feyissa ◽  
Justin Renaud ◽  
Vida Nasrollahi ◽  
Susanne Kohalmi ◽  
Abdelali Hannoufa
Keyword(s):  
Drought Stress ◽  
Metal Ion ◽  
Interaction Analysis ◽  
Expression Patterns ◽  
Specific Gene ◽  
Primary Metabolism ◽  
Dependent Manner ◽  
Protein Protein Interaction ◽  
Electron Transport Chains ◽  
Transcript Profiles

Abstract Background We previously reported on the interplay between miR156/SPL13 and WD40-1/DFR to improve response to drought stress in alfalfa (Medicago sativa L.). Here we aimed to investigate whether the role of miR156/SPL13 module in drought response is tissue-specific, and to identify SPL13-interacting proteins. We analyzed the global transcript profiles of leaf, stem, and root tissues of one-month old RNAi-silenced SPL13 (SPL13RNAi) alfalfa plants exposed to drought stress and conducted protein-protein interaction analysis to identify SPL13 interacting partners . Result Transcript analysis combined with weighted gene co-expression network analysis showed tissue and genotype-specific gene expression patterns. Moreover, pathway analysis of stem-derived differentially expressed genes (DEG) revealed upregulation of genes associated with stress mitigating primary and specialized metabolites, whereas genes associated with photosynthesis light reactions were silenced in SPL13RNAi plants. Leaf-derived DEG were attributed to enhanced light reactions, largely photosystem I, II, and electron transport chains, while roots of SPL13RNAi plants upregulated transcripts associated with metal ion transport, carbohydrate, and primary metabolism. Using immunoprecipitation combined with mass spectrometry (IPMS) we showed that SPL13 interacts with proteins involved in photosynthesis, specialized metabolite biosynthesis, and stress tolerance. Conclusions We conclude that the miR156/SPL13 module mitigates drought stress in alfalfa by regulating molecular and physiological processes in a tissue-dependent manner.

scholarly journals Synovial Sarcoma Translocation (SYT) Encodes a Nuclear Receptor Coactivator

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3892-3899 ◽  
Author(s):  
Toshiharu Iwasaki ◽  
Noriyuki Koibuchi ◽  
William W. Chin
Keyword(s):  
Synovial Sarcoma ◽  
Hormone Receptors ◽  
Rna Binding ◽  
Thyroid Hormone Receptor ◽  
Single Gene ◽  
Binding Motif ◽  
Dependent Manner ◽  
Interacting Protein ◽  
C Terminus ◽  
The Brain

Abstract We previously cloned and characterized a novel RNA-binding motif-containing coactivator, named coactivator activator (CoAA), as a thyroid hormone receptor-binding protein-interacting protein using a Sos-Ras yeast two-hybrid screening system. A database search revealed that CoAA is identical with synovial sarcoma translocation (SYT)-interacting protein. Thus, we hypothesized that SYT could also function as a coactivator. Subsequently, we isolated a cDNA encoding a larger isoform of SYT, SYT-long (SYT-L), from the brain and liver total RNA using RT-PCR. SYT-L possesses an additional 31 amino acids in its C terminus compared with SYT, suggesting that these two SYT isoforms may be expressed from two mRNAs produced by alternative splicing of a transcript from a single gene. By Northern blot analysis, we found that SYT-L mRNA is expressed in several human embryonic tissues, such as the brain, liver, and kidney. However, we could not detect SYT-L in adult tissues. Glutathione-S-transferase pull-down studies showed that SYT binds to the C-terminus of CoAA, but not to the coactivator modulator. Both isoforms of SYT function as transcriptional coactivators of nuclear hormone receptors in a ligand- and dose-dependent manner in CV-1, COS-1, and JEG-3 cells. However, the pattern of transactivation was different between SYT and SYT-L among these cells. SYT synergistically activates transcription with CoAA. In addition, SYT activates transcription through activator protein-1, suggesting that SYT may function as a general coactivator. These results indicate that SYT activates transcription, possibly through CoAA, to interact with the histone acetyltransferase complex.

scholarly journals Application of the 3'-Untranslated Region of Messenger RNA from Measles Virus Matrix Protein as an RNA Stabilizer: Implications in Pharmaceutical Biotechnology

2019 ◽  
Vol 9 (1) ◽  
pp. 53
Author(s):  
Marzieh Marzbany ◽  
Fatemeh Ghassemi ◽  
Mahsa Rasekhian
Keyword(s):  
Mrna Stability ◽  
Messenger Rna ◽  
Untranslated Region ◽  
Measles Virus ◽  
Matrix Protein ◽  
Rna Binding ◽  
Rna Stability ◽  
Minimum Free Energy ◽  
Expression Vectors ◽  
Dependent Manner

BACKGROUND: The market for the use of recombinant proteins for medical applications has been increasing in recent years. In many cases including fast production of significant amounts of protein for research purposes, transient transfection is the method of choice. In this regard expression vectors are one of the decisive factors in the cost-effectiveness of the production process. The genetic elements found in the 3’untranslated region (UTR) of mRNA expressed by such vectors, play an essential role in determining its stability and thus in the efficiency of the process. METHODS: In this study, the 3'UTR of matrix protein from the Measles Virus (MV) was used to construct a reporter plasmid containing Enhanced Green Fleurocent Protein (EGFP). The reporter construct was transfected into three cell lines. The effect of 3'UTR on mRNA stability was evaluated by real-time PCR. Secondary structure of the mrna was predicted based on minimum free energy. 3'UTR was analyzed in silico for the presence of binding motifs for trans-acting elements with known effects on RNA stability. RESULTS: Addition of 3’UTR of MV matrix protein sequence to the 3’ end of the mRNA, increased the EGFP- mRNA stability in time and cell-dependent manner. Analysis for the presence of known cis-acting motifs in 3’UTR indicated the presence of two PABPC1 binding sites, an RNA-binding protein, known for its stability and translation enhancing effects. CONCLUSION: Our results verified the potential of the 3'UTR region of matrix protein mRNA for improvement of transient recombinant protein production and vector design for mammalian cell hosts.

scholarly journals Characterization and analysis of the transcriptome in Arapaima gigas using multi-tissue RNA-sequencing

2020 ◽  
Author(s):  
Danilo L. Martins ◽  
Leonardo R. S. Campos ◽  
André M. Ribeiro-dos-Santos ◽  
Ana Carolina M. F. Coelho ◽  
Renata L. Dantas ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Expression Patterns ◽  
Gene Clusters ◽  
Molecular Networks ◽  
Specific Gene ◽  
Protein Coding ◽  
Tissue Specific ◽  
Functional Studies ◽  
A Genome ◽  
Arapaima Gigas

AbstractArapaima gigas is a giant bony tongue air-breathing fish, and a promising species for aquaculture due to its particular features. However, there is still a lack of information on its biology and few transcriptome studies are available. Our aim was to characterize the transcriptome of arapaima in order to shed light on molecular networks contributing to its unique traits. Through RNA-sequencing, we generated a transcriptome from eight tissues (brain, pituitary, heart, muscle, kidney, lung, ovary, and testis) collected from arapaima adults specimens. Using a genome-guided strategy associated with homologous protein evidence, 57,706 transcripts were assembled, which aligned to 23,353 high confidence protein-coding genes. The analysis revealed a global view of expression patterns, as well as it allowed us to identify tissue-specific gene clusters, transcription factors within the clusters, and to compare expression patterns between male and female. These analyses has generated tissue-specific and sex-biased transcriptome profiles, which will be helpful to understand its molecular biology, evolution, and also guide future functional studies of the arapaima.

scholarly journals The RNA-binding protein Puf5 contributes to buffering of mRNA upon chromatin-mediated changes in nascent transcription

2021 ◽  
Author(s):  
David Z. Kochan ◽  
Julia S. P. Mawer ◽  
Jennifer Massen ◽  
Kiril Tishinov ◽  
Swati Parekh ◽  
...  
Keyword(s):  
Chromatin Structure ◽  
Rna Binding ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Feedback Mechanisms ◽  
Mrna Targets ◽  
Genome Wide ◽  
A Genome ◽  
Mrna Surveillance ◽  
Global Increase

Gene expression involves regulation of chromatin structure and transcription, as well as processing of the transcribed mRNA. While there are feedback mechanisms, it is not clear whether these include crosstalk between chromatin architecture and mRNA decay. To address this, we performed a genome-wide genetic screen using a yeast strain harbouring the H3K56A mutation known to perturb chromatin structure and nascent transcription. We identified Puf5 as essential in an H3K56A background. Depletion of Puf5 in this background leads to downregulation of Puf5 targets. We suggest that Puf5 plays a role in post-transcriptional buffering of mRNAs and support this by transcriptional shutoff experiments in which Puf5 mRNA targets are degraded slower in H3K56A compared to wildtype. Finally, we show that post-transcriptional buffering of Puf5 targets is widespread and does not occur only in an H3K56A mutant, but also in an H3K4R background, which leads to a global increase in nascent transcription. Our data suggest that Puf5 determines the fate of its mRNA targets in a context-dependent manner acting as an mRNA surveillance hub balancing de-regulated nascent transcription to maintain physiological mRNA levels.

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