Conserved patterns of alternative splicing in response to cold acclimation in fish

2018 ◽  
Author(s):  
Timothy M. Healy ◽  
Patricia M. Schulte
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Phenotypic Plasticity ◽  
Cold Acclimation ◽  
Gasterosteus Aculeatus ◽  
Expression Patterns ◽  
Functional Enrichment ◽  
Cold Temperatures ◽  
Qualitative Changes

AbstractPhenotypic plasticity is an important aspect of an organism’s response to environmental change that often requires the modulation of gene expression. These changes in gene expression can be quantitative as a result of increases or decreases in the amounts of specific transcripts, or qualitative as a result of the expression of alternative transcripts from the same gene (e.g., via alternative splicing of pre-mRNAs). Although the role of quantitative changes in gene expression in phenotypic plasticity is well known, relatively few studies have examined the role of qualitative changes. Here, we use skeletal muscle RNA-seq data from Atlantic killifish (Fundulus heteroclitus), threespine stickleback (Gasterosteus aculeatus) and zebrafish (Danio rerio) to investigate the extent of qualitative changes in gene expression in response to cold. Fewer genes demonstrated alternative splicing than differential expression as a result of cold acclimation; however, differences in splicing were detected for between 426 and 866 genes depending on species, indicating that large numbers of qualitative changes in gene expression are associated with cold acclimation. Many of these alternatively spliced genes were also differentially expressed, and there was functional enrichment for involvement in muscle contraction among the genes demonstrating qualitative changes in response to cold acclimation. Additionally, there was a common group of 29 genes with cold-acclimation-mediated changes in splicing in all three species, suggesting that there may be a conserved set of genes with expression patterns that respond qualitatively to prolonged cold temperatures across fishes.Summary statementQualitative changes in gene expression, such as those mediated by alternative splicing of mRNAs, are involved in phenotypic plasticity in response to prolonged cold acclimation in ectothermic animals

Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 2090-2093 ◽  
Author(s):  
Dirk Kienle ◽  
Axel Benner ◽  
Alexander Kröber ◽  
Dirk Winkler ◽  
Daniel Mertens ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Expression Of Genes ◽  
Vh Genes ◽  
Signaling Activation

The mutation status and usage of specific VH genes such as V3-21 and V1-69 are potentially independent pathogenic and prognostic factors in chronic lymphocytic leukemia (CLL). To investigate the role of antigenic stimulation, we analyzed the expression of genes involved in B-cell receptor (BCR) signaling/activation, cell cycle, and apoptosis control in CLL using these specific VH genes compared to VH mutated (VH-MUT) and VH unmutated (VH-UM) CLL not using these VH genes. V3-21 cases showed characteristic expression differences compared to VH-MUT (up: ZAP70 [or ZAP-70]; down: CCND2, P27) and VH-UM (down: PI3K, CCND2, P27, CDK4, BAX) involving several BCR-related genes. Similarly, there was a marked difference between VH unmutated cases using the V1-69 gene and VH-UM (up: FOS; down: BLNK, SYK, CDK4, TP53). Therefore, usage of specific VH genes appears to have a strong influence on the gene expression pattern pointing to antigen recognition and ongoing BCR stimulation as a pathogenic factor in these CLL subgroups.

Abstract P460: Role Of Hopx In Antiretroviral Drugs Induced Cardiac Hypertrophy And Epigenetic Modification

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Shiridhar Kashyap ◽  
Olena Kondrachuk ◽  
Manish K Gupta
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Cardiac Dysfunction ◽  
Epigenetic Modification ◽  
Trichostatin A ◽  
Antiretroviral Drugs ◽  
Functional Enrichment ◽  
Hiv Patients ◽  
Acetylation Level

Background: Heart failure is the one of the leading causes of death in HIV patients. Application ofantiretroviral therapy (ART) raise the life expectancy of HIV patients, but survival population show higherrisk of cardiovascular disorder. The aim of this study is to understand the underlying molecular mechanismof antiretroviral drugs (ARVs) induced cardiac dysfunction in HIV patients. Method and Results: To determine the mechanism of ARVs induced cardiac dysfunction, we performeda global transcriptomic profiling in primary cardiomyocytes treated with ARVs. Differentially expressedgenes were identified by DESeq2. Functional enrichment analysis of differentially expressed genes wereperformed using clusterProfiler R and ingenuity pathway analysis. Our data show that ARVs treatmentcauses upregulation of several biological function associated with cardiotoxicity and heart failure.Interestingly, we found that ARV drugs treatment significantly upregulates the expression of a set of genesinvolved cardiac enlargement and hypertrophy in the heart. Global gene expression data were validated inthe cardiac tissue isolated from the HIV patients having history of ART treatment. Interestingly, we foundthat the homeodomain-containing only protein homeobox (HOPX) expression was significantly increasedin transcriptional and translational level in cardiomyocytes treated with ARV drugs as well as in heart tissueof ART treated HIV patients. Further, we performed adenovirus mediated gain in and siRNA mediatedknockdown approach to determine the role of HOPX in ARVs mediated cardiac hypertrophy and epigeneticmodifications. Mechanistically, we found that HOPX expression level plays a key role in ARV drugsmediated increased cardiomyocytes cell size and reduced acetylation level of histone 3 at lysine 9 and lysine27. Furthermore, we found that knockdown of HOPX gene expression blunted the hypertrophy effect ofARV drugs in cardiomyocytes. It is known that HOPX reduces cellular acetylation level through interactionwith HDAC2. In our study, we found that histone deacetylase inhibitor Trichostatin A can restore cellularacetylation level in presence of ARVs. Conclusion: ART treatment causes cardiotoxicity through regulation of fatal gene expression incardiomyocytes and in adult heart. Additionally, we found that HOPX expression is critical in ARVsmediated cardiomyocytes remodeling and epigenetic modification.

scholarly journals Colon Cancer and SARS-CoV-2: Impact of ACE2 Expression in Susceptibility to COVID-19

2020 ◽  
Author(s):  
Mohsen Ahmadi ◽  
Negin Saffarzadeh ◽  
Mohammad Amin Habibi ◽  
Fatemeh Hajiesmaeili ◽  
Nima Rezaei
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Immune Cell ◽  
Expression Patterns ◽  
Methylation Status ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Survival Outcomes ◽  
Immune Cell Infiltration ◽  
Ace2 Gene

AbstractNovel coronavirus disease (COVID-19) pandemic has become a global health emergency. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with angiotensin-converting enzyme 2 (ACE2) to enter the cells and infects diverse human tissues. It has been reported that a few conditions, including cancer, predispose individuals to SARS-CoV-2 infection and severe form of COVID-19. These findings led us to evaluate the susceptibility of colon adenocarcinoma (COAD) patients to SARS-CoV-2 infection by investigation of ACE2 expression in their tumor tissues. The expression analysis revealed that both mRNA and protein levels of ACE2 had increased in colon cancer samples than normal group. Next, the prognosis analysis has indicated that the upregulation of ACE2 was not correlated with patient survival outcomes. Further assessment displayed the hypomethylation of the ACE2 gene promoter in COAD patients. Surprisingly, this methylation status has a strong negative correlation with ACE2 gene expression. The functional enrichment analysis of the genes that had similar expression patterns with ACE2 in colon cancer tissues demonstrated that they mainly enriched in Vitamin digestion and absorption, Sulfur relay system, and Fat digestion and absorption pathways. Finally, we found that ACE2 gene expression had a significant association with the immune cell infiltration levels in COAD patients. In conclusion, it has plausible that COAD patients are more likely to be infected with SARS-CoV-2 and experience severe injuries. Moreover, COVID-19 would bring unfavorable survival outcomes of patients with colon cancer by the way of immune cell infiltration linked process. The present study highlights the importance of preventive actions for COAD patients during the COVID-19 pandemic.

scholarly journals Alternative Splicing of Transcription Factors' Genes: Beyond the Increase of Proteome Diversity

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
David Talavera ◽  
Modesto Orozco ◽  
Xavier de la Cruz
Keyword(s):  
Transcription Factors ◽  
Alternative Splicing ◽  
Expression Patterns ◽  
Developmental Changes ◽  
Functional Families ◽  
Transcription Regulators ◽  
Alternatively Spliced ◽  
The Impact ◽  
Human And Mouse

Functional modification of transcription regulators may lead to developmental changes and phenotypical differences between species. In this work, we study the influence of alternative splicing on transcription factors in human and mouse. Our results show that the impact of alternative splicing on transcription factors is similar in both species, meaning that the ways to increase variability should also be similar. However, when looking at the expression patterns of transcription factors, we observe that they tend to diverge regardless of the role of alternative splicing. Finally, we hypothesise that transcription regulation of alternatively spliced transcription factors could play an important role in the phenotypical differences between species, without discarding other phenomena or functional families.

scholarly journals Cold Acclimation of the Thermoacidophilic Red Alga Galdieria sulphuraria: Changes in Gene Expression and Involvement of Horizontally Acquired Genes

2018 ◽  
Vol 60 (3) ◽  
pp. 702-712 ◽  
Author(s):  
Alessandro W Rossoni ◽  
Gerald Sch�nknecht ◽  
Hyun Jeong Lee ◽  
Ryan L Rupp ◽  
Samantha Flachbart ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Cold Acclimation ◽  
Growth Temperature ◽  
Toxic Metal ◽  
Optimal Growth ◽  
Red Alga ◽  
Galdieria Sulphuraria ◽  
Cold Temperatures

Abstract Galdieria sulphuraria is a unicellular red alga that lives in hot, acidic, toxic metal-rich, volcanic environments, where few other organisms survive. Its genome harbors up to 5% of genes that were most likely acquired through horizontal gene transfer. These genes probably contributed to G.sulphuraria’s adaptation to its extreme habitats, resulting in today’s polyextremophilic traits. Here, we applied RNA-sequencing to obtain insights into the acclimation of a thermophilic organism towards temperatures below its growth optimum and to study how horizontally acquired genes contribute to cold acclimation. A decrease in growth temperature from 42�C/46�C to 28�C resulted in an upregulation of ribosome biosynthesis, while excreted proteins, probably components of the cell wall, were downregulated. Photosynthesis was suppressed at cold temperatures, and transcript abundances indicated that C-metabolism switched from gluconeogenesis to glycogen degradation. Folate cycle and S-adenosylmethionine cycle (one-carbon metabolism) were transcriptionally upregulated, probably to drive the biosynthesis of betaine. All these cold-induced changes in gene expression were reversible upon return to optimal growth temperature. Numerous genes acquired by horizontal gene transfer displayed temperature-dependent expression changes, indicating that these genes contributed to adaptive evolution in G.sulphuraria.

scholarly journals Identification of Differentially Expressed MicroRNAs and Their Potential Target Genes in Adipose Tissue from Pigs with Highly Divergent Backfat Thickness

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 624
Author(s):  
Kai Xing ◽  
Xitong Zhao ◽  
Yibing Liu ◽  
Fengxia Zhang ◽  
Zhen Tan ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Patterns ◽  
Fat Deposition ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Backfat Thickness ◽  
P Value ◽  
Sibling Pairs ◽  
Differentially Expressed Mirnas

Fatty traits are very important in pig production. However, the role of microRNAs (miRNAs) in fat deposition is not clearly understood. In this study, we compared adipose miRNAs from three full-sibling pairs of female Landrace pigs, with high and low backfat thickness, to investigate the associated regulatory network. We obtained an average of 17.29 million raw reads from six libraries, 62.27% of which mapped to the pig reference genome. A total of 318 pig miRNAs were detected among the samples. Among them, 18 miRNAs were differentially expressed (p-value < 0.05, |log2fold change| ≥ 1) between the high and low backfat groups; 6 were up-regulated and 12 were down-regulated. Functional enrichment of the predicted target genes of the differentially expressed miRNAs, indicated that these miRNAs were involved mainly in lipid and carbohydrate metabolism, and glycan biosynthesis and metabolism. Comprehensive analysis of the mRNA and miRNA transcriptomes revealed possible regulatory relationships for fat deposition. Negatively correlated mRNA–miRNA pairs included miR-137–PPARGC1A, miR-141–FASN, and miR-122-5p–PKM, indicating these interactions may be key regulators of fat deposition. Our findings provide important insights into miRNA expression patterns in the backfat tissue of pig and new insights into the regulatory mechanisms of fat deposition in pig.

scholarly journals Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1108
Author(s):  
Dina Hesham ◽  
Shahenda El-Naggar
Keyword(s):  
Cell Cycle ◽  
Alternative Splicing ◽  
Wnt Signaling Pathway ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Embryonal Tumor ◽  
Alternative Splicing Events ◽  
Regulation Of Cell Cycle

Embryonal tumor with multilayered rosettes (ETMR) is an aggressive and rare pediatric embryonal brain tumor. Amplification of C19MC microRNA cluster and expression of LIN28 are distinctive features of ETMR. Despite the increasing efforts to decipher ETMR, the biology remains poorly understood. To date, the role of aberrant alternative splicing in ETMR has not been thoroughly investigated. In the current study, a comprehensive analysis was performed on published unprocessed RNA-seq reads of tissue-matched ETMR and fetal controls datasets. Gene expression was quantified in samples using Kallisto/sleuth pipeline. For the alternative splicing analysis, STAR, SplAdder and rMATS were used. Functional enrichment analysis was subsequently performed using Metascape. The expression analysis identified a total of 3622 differentially expressed genes (DEGs) between ETMR and fetal controls while 1627 genes showed differential alternative splicing patterns. Interestingly, genes with significant alternative splicing events in ETMR were identified to be involved in signaling pathways such as ErbB, mTOR and MAPK pathways as well as ubiquitin-mediated proteolysis, cell cycle and autophagy. Moreover, up-regulated DEGs with alternative splicing events were involved in important biological processes including nuclear transport, regulation of cell cycle and regulation of Wnt signaling pathway. These findings highlight the role of aberrant alternative splicing in shaping the ETMR tumor landscape, and the identified pathways constitute potential therapeutic targets.

Defining The Role Of Microrna-146a In B Cell Lymphomagenesis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3805-3805
Author(s):  
Jorge Contreras ◽  
Jayanth Kumar Palanichamy ◽  
Tiffany Tran ◽  
Dinesh S. Rao
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
Significant Proportion ◽  
B Cell Lymphoma ◽  
Gene Expression Patterns

Abstract Diffuse large B cell lymphoma (DLBCL) is one of the most common Non-Hodgkin lymphomas among adults. It is a heterogeneous disease characterized by multiple mutations and translocations. Gene expression profiling studies have revealed several characteristic gene expression patterns, with two main patterns emerging, namely Germinal Center(GC) type, and Activated B Cell (ABC) type. ABC-type DLBCL shows gene expression patterns that resemble activated B-cells, with increased expression of anti-apoptotic, and pro-proliferative genes. Critically, upregulation of the NF-κB the pathway is a hallmark of ABC-type DLBCL and has been shown to be necessary for survival, and is caused by several different mutations at different levels within the pathway. Recent work has revealed the critical importance of a new class of small RNA molecules, namely microRNAs, in gene regulation. Of these, microRNA-146a (miR-146a) was discovered as an NF-κB induced microRNA that plays a role as a negative feedback regulator of this pathway by targeting adaptor proteins. To further characterize miR-146a, mice deficient for this miRNA were created, and were found to develop lymphadenopathy, splenomegaly, and myeloid proliferation. As expected, immune cells in these mice have an upregulated NF-κB pathway and many of the phenotypes can be ameliorated by inhibition of the NF-κB pathway. Importantly, a significant proportion of the animals develop B-cell lymphoma at older ages. In this study, we examined the role of miR-146a in the development of malignancy in B-cells. To accelerate the role of miR-146a in tumor formation we overlaid the miR-146a deficient allele onto the Eμ-Myc like mouse model. Eμ-Myc mice develop tumors on average by 14weeks of age. The transgenic status of animals was verified by genotyping, RNA and protein expression analyses. miR-146a sufficient and deficient animals on the Eμ-Myc background were followed for tumor latency by peripheral blood analysis and careful physical examination. Based on approved humane criteria for animal discomfort, animals were sacrificed and hematopoietic tissue was harvested for analysis. Mice deficient for miR-146a had a statistically reduced survival in comparison with miR-146a sufficient animals with a p-value of .0098 (Kaplan Meir survival analysis). Complete Blood Count of animals at time of death revealed an increase leukemia presentation in the miR-146a deficient background. FACS analysis of tumor tissue from both groups revealed an increase in the number of IgM positive tumors in the miR-146a-deficient background indicating skewing towards more mature B cell neoplasms when miR-146a is lacking. Lineage analysis of tumors verified them to be of B cell origin although a subset of miR-146a sufficient tumors had higher numbers of infiltrating myeloid cells compared to deficient animals. Furthermore, histologic analysis of hematopoietic organs showed that while infiltration remained similar in kidneys and liver, more spleens in the miR-146a deficient background tended to be less involved. Our extensive histopathologic and immunophenotypic analyses indicate that miR-146a deficiency drives a more aggressive malignant phenotype in the B-cell lineage. In keeping with this, our profiling studies of human DLBCL suggest that a subset of DLBCL show decreased expression of miR-146a. We are currently examining the status of NF-κB in the murine tumors and using high throughput sequencing approaches to delineate gene expression differences between miR-146a sufficient and deficient tumors. We anticipate the discovery of novel gene targets of miR-146a and expect that these studies will lead to improved diagnostic and therapeutic options for patients of B-cell malignancies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Correlation between Bacillus subtilis scoC Phenotype and Gene Expression Determined Using Microarrays for Transcriptome Analysis

2001 ◽  
Vol 183 (24) ◽  
pp. 7329-7340 ◽  
Author(s):  
Robert Caldwell ◽  
Ron Sapolsky ◽  
Walter Weyler ◽  
Randal R. Maile ◽  
Stuart C. Causey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Expression Patterns ◽  
Global Scale ◽  
Complete Sequence ◽  
Dna Arrays ◽  
Genome Wide ◽  
Genes Encoding ◽  
Nucleoside Metabolism

ABSTRACT The availability of the complete sequence of the Bacillus subtilis chromosome (F. Kunst et al., Nature 390:249–256, 1997) makes possible the construction of genome-wide DNA arrays and the study of this organism on a global scale. Because we have a long-standing interest in the effects of scoC on late-stage developmental phenomena as they relate toaprE expression, we studied the genome-wide effects of ascoC null mutant with the goal of furthering the understanding of the role of scoC in growth and developmental processes. In the present work we compared the expression patterns of isogenic B. subtilis strains, one of which carries a null mutation in the scoC locus (scoC4). The results obtained indicate thatscoC regulates, either directly or indirectly, the expression of at least 560 genes in the B. subtilisgenome. ScoC appeared to repress as well as activate gene expression. Changes in expression were observed in genes encoding transport and binding proteins, those involved in amino acid, carbohydrate, and nucleotide and/or nucleoside metabolism, and those associated with motility, sporulation, and adaptation to atypical conditions. Changes in gene expression were also observed for transcriptional regulators, along with sigma factors, regulatory phosphatases and kinases, and members of sensor regulator systems. In this report, we discuss some of the phenotypes associated with the scoCmutant in light of the transcriptome changes observed.

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