scholarly journals Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Jin Li ◽  
Peng Yu
Keyword(s):  
Alternative Splicing ◽  
Transcriptome Analysis ◽  
Regulatory Network ◽  
Splicing Factors ◽  
Genome Wide

scholarly journals Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis

2018 ◽  
Author(s):  
Jin Li ◽  
Peng Yu
Keyword(s):  
Alternative Splicing ◽  
Computational Analysis ◽  
Potential Role ◽  
Exon Skipping ◽  
Chronic Inflammatory Disease ◽  
Splicing Factors ◽  
The Novel ◽  
Rna Seq ◽  
Genome Wide

AbstractPsoriasis is a chronic inflammatory disease that affects the skin, nails, and joints. For understanding the mechanism of psoriasis, though, alternative splicing analysis has received relatively little attention in the field. Here, we developed and applied several computational analysis methods to study psoriasis. Using psoriasis mouse and human datasets, our differential alternative splicing analyses detected hundreds of differential alternative splicing changes. Our analysis of conservation revealed many exon-skipping events conserved between mice and humans. In addition, our splicing signature comparison analysis using the psoriasis datasets and our curated splicing factor perturbation RNA-Seq database, SFMetaDB, identified nine candidate splicing factors that may be important in regulating splicing in the psoriasis mouse model dataset. Three of the nine splicing factors were confirmed upon analyzing the human data. Our computational methods have generated predictions for the potential role of splicing in psoriasis. Future experiments on the novel candidates predicted by our computational analysis are expected to provide a better understanding of the molecular mechanism of psoriasis and to pave the way for new therapeutic treatments.

scholarly journals An Arabidopsis long noncoding RNA modulates the transcriptome through interactions with a network of splicing factors

2020 ◽  
Author(s):  
Richard Rigo ◽  
Jérémie Bazin ◽  
Natali Romero-Barrios ◽  
Michaël Moison ◽  
Leandro Lucero ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Root Formation ◽  
Noncoding Rnas ◽  
Dynamic Network ◽  
Splicing Factors ◽  
Genome Wide ◽  
A Minor ◽  
Conserved Core

ABSTRACTAlternative splicing (AS) is a major source of transcriptome and proteome diversity in higher organisms. Long noncoding RNAs (lncRNAs) have emerged as regulators of AS through a range of molecular mechanisms. In Arabidopsis thaliana, the AS regulators NSRa and b, which affect auxin-driven lateral root formation, can interact with the ALTERNATIVE SPLICING COMPETITOR (ASCO) lncRNA. Here, we analyzed the effect of the knockdown and overexpression of ASCO at genome-wide level and found a high number of deregulated and differentially spliced genes, related to flagellin responses and biotic stress. In agreement, roots from ASCO-knocked down plants are more sensitive to flagellin. Surprisingly, only a minor subset of genes overlapped with the AS defects of the nsra/b double mutant. Using biotin-labelled oligonucleotides for RNA-mediated ribonucleoprotein purification, we found that ASCO binds to the highly conserved core spliceosome component PRP8a. ASCO deregulation impairs the recognition of specific flagellin-related transcripts by PRP8a and SmD1b, another spliceosome component, suggesting that ASCO function regulates AS through the interaction with multiple splicing factors. Hence, lncRNAs may interact in a dynamic network with many splicing factors to modulate transcriptome reprogramming in eukaryotes.

scholarly journals Genome-wide identification, transcriptome analysis and alternative splicing events of Hsf family genes in maize

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Huaning Zhang ◽  
Guoliang Li ◽  
Cai Fu ◽  
Shuonan Duan ◽  
Dong Hu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Transcriptome Analysis ◽  
Genome Wide ◽  
Alternative Splicing Events

scholarly journals Splicing Programs and Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Sophie Germann ◽  
Lise Gratadou ◽  
Martin Dutertre ◽  
Didier Auboeuf
Keyword(s):  
Alternative Splicing ◽  
Gene Networks ◽  
Large Scale ◽  
Splicing Factors ◽  
Novel Technologies ◽  
Normal Tissues ◽  
Genome Wide ◽  
Splicing Variants ◽  
Cancer Initiation ◽  
Genetic Mechanisms

Numerous studies report splicing alterations in a multitude of cancers by using gene-by-gene analysis. However, understanding of the role of alternative splicing in cancer is now reaching a new level, thanks to the use of novel technologies allowing the analysis of splicing at a large-scale level. Genome-wide analyses of alternative splicing indicate that splicing alterations can affect the products of gene networks involved in key cellular programs. In addition, many splicing variants identified as being misregulated in cancer are expressed in normal tissues. These observations suggest that splicing programs contribute to specific cellular programs that are altered during cancer initiation and progression. Supporting this model, recent studies have identified splicing factors controlling cancer-associated splicing programs. The characterization of splicing programs and their regulation by splicing factors will allow a better understanding of the genetic mechanisms involved in cancer initiation and progression and the development of new therapeutic targets.

scholarly journals Comprehensive network analysis reveals alternative splicing-related lncRNAs in hepatocellular carcinoma

2019 ◽  
Author(s):  
Junqing Wang ◽  
Yixin Chen ◽  
Keli Xu ◽  
Yin-yuan Mo ◽  
Yunyun Zhou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Alternative Splicing ◽  
Rna Splicing ◽  
Normal Liver ◽  
Splicing Factors ◽  
Primary Concern ◽  
Rna Seq ◽  
Genome Wide ◽  
Tumorigenesis And Progression ◽  
Extensive Collection

AbstractA number of recent studies have highlighted the findings that certain lncRNAs are associated with alternative splicing (AS) in tumorigenesis and progression. Although existing work showed the importance of linking certain misregulations of RNA splicing with lncRNAs, a primary concern is the lack of genome-wide comprehensive analysis for their associations.We analyzed an extensive collection of RNA-seq data, quantified 198,619 isoform expressions, and found systematic isoform usage changes between hepatocellular carcinoma (HCC) and normal liver tissue. We identified a total of 1375 splicing switched isoforms and further analyzed their biological functions.To predict which lncRNAs are associated with these AS genes, we integrated the co-expression networks and epigenetic interaction networks collected from text mining and database searching, linking lncRNA modulators such as splicing factors, transcript factors, and miRNAs with their targeted AS genes in HCC. To model the heterogeneous networks in a single framework, we developed a multi-graphic random walk (RWMG) network method to prioritize the lncRNAs associated with AS in HCC. RWMG showed a good performace evaluated by ROC curve based on cross-validation and bootstrapping strategy.As a summary, we identified 31 AS-related lncRNAs including MALAT1 and HOXA11-AS, which have been reported before, as well as some novel lncRNAs such as DNM1P35, HAND2-AS1, and DLX6-AS1. Survival analysis further confirmed the clinical significance of identified lncRNAs.

scholarly journals Networks of Splice Factor Regulation by Unproductive Splicing Coupled With Nonsense Mediated mRNA Decay

2020 ◽  
Author(s):  
Anna Desai ◽  
Zhiqiang Hu ◽  
Courtney E. French ◽  
James P. B. Lloyd ◽  
Steven E. Brenner
Keyword(s):  
Transcription Factors ◽  
Alternative Splicing ◽  
Regulatory Network ◽  
Mrna Decay ◽  
Current Knowledge ◽  
Interaction Network ◽  
Splicing Factor ◽  
Splicing Factors ◽  
Extensive Literature ◽  
Nonsense Mediated Mrna Decay

AbstractBackgroundNonsense mediated mRNA decay (NMD) is an RNA surveillance pathway that degrades aberrant transcripts harboring premature termination codons. This pathway, in conjunction with alternative splicing, regulates gene expression post-transcriptionally. Nearly all serine and arginine-rich (SR) proteins and many heterogeneous nuclear ribonucleoproteins (hnRNPs) produce isoforms that can be degraded by the NMD pathway. Many splicing factors have been reported to be regulated via alternative splicing coupled to NMD. However, it is still uncharacterized that to what extent NMD contributes to the regulation of splicing factors.ResultsHere, we characterized a regulatory network of splicing factors through alternative splicing coupled to NMD. Based upon an extensive literature search, we first assembled a network that encompasses the current knowledge of splice factors repressing or activating the expression of other splicing factors through alternative splicing coupled to NMD. This regulatory network is limited, including just a handful of well-studied splicing factors. To gain a more global and less biased overview, we examined the splicing factor-mRNA interactions from public crosslinking-immunoprecipitation (CLIP)-seq data, which provides information about protein–RNA interactions. A network view of these interactions reveals extensive binding among splicing regulators. We also found that splicing factors bind more frequently to transcripts of other splicing factors than to other genes. In addition, many splicing factors are targets of NMD, and might be regulated via alternative splicing coupled to NMD, which is demonstrated by the significant overlap between the experimental network and eCLIP-network. We found that hierarchy of the splicing-factor interaction network differs from the hierarchy observed for transcription factors.ConclusionThe extensive interaction between splicing factors and transcripts of other splicing factors suggests that the potential regulation via alternative splicing coupled with NMD is widespread. The splicing factor regulation is fundamentally different from that of transcription factors.

scholarly journals Genome-wide analyses of the prognosis-related mRNA alternative splicing landscape and novel splicing factors based on large-scale low grade glioma cohort

Aging ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 13684-13700
Author(s):  
Wang-Rui Liu ◽  
Chuan-Yu Li ◽  
Wen-Hao Xu ◽  
Xiao-Juan Liu ◽  
Hai-Dan Tang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Large Scale ◽  
Low Grade Glioma ◽  
Splicing Factors ◽  
Low Grade ◽  
Genome Wide

Splicing factors: Insights into their regulatory network in alternative splicing in cancer

2020 ◽  
Author(s):  
Jun-Xian Du ◽  
Gui-Qi Zhu ◽  
Jia-Liang Cai ◽  
Biao Wang ◽  
Yi-Hong Luo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Regulatory Network ◽  
Splicing Factors

scholarly journals Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases

2018 ◽  
Vol 48 (3) ◽  
pp. 1355-1368 ◽  
Author(s):  
Rong-quan He ◽  
Xian-guo Zhou ◽  
Qiao-yong Yi ◽  
Cai-wang Deng ◽  
Jia-min Gao ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Urothelial Carcinoma ◽  
Risk Score ◽  
Regulatory Network ◽  
Pearson Correlation ◽  
Risk Scores ◽  
Pathway Enrichment Analysis ◽  
Splicing Factors ◽  
Bladder Urothelial Carcinoma ◽  
Alternative Splicing Events

Background/Aims: Increasing evidences indicated the important roles of alternative splicing in the progression and prognosis of bladder urothelial carcinoma (BLCA). However, most previous research has focused on one or several alternative splicing events, without a comprehensive evaluation of the prognostic value of splicing events in BLCA. In this study, we aimed to determine risk scores for predicting prognosis of BLCA patients based on splicing events. Methods: RNA-sequencing data and clinical information of BLCA patients were downloaded from The Cancer Genome Atlas, and data of splicing events were obtained from the SpliceSeq database. Univariate and multivariate Cox regression analyses were employed to identify survival-associated alternative spicing events (SASEs) and to calculate risk scores. Protein-protein interaction analysis of genes of the SASEs was performed using STRING, a database of known and predicted protein-protein interactions, and pathway enrichment analysis of the genes was implemented using the Database for Annotation, Visualization and Integrated Discovery (version 6.8). Receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to evaluate the clinical significance of genes from the SASEs for building a risk score in BLCA. Correlation between splicing events of splicing factors and non-splicing factors were analyzed with Pearson correlation coefficient. A potential regulatory network was then built using Cytoscape 3.5. Results: In total, 39,508 alternative splicing events in 317 patients with BLCA were analyzed, including 4,632 SASEs. The area under the curve of the ROC of risk score (all) was 0.748 for predicting survival status of BLCA patients. Low- and high-risk score groups classified using the median “risk score (all)” value displayed remarkably different survival time (Low vs. High = 3304.841±239.758 vs 1198.614±152.460 days). The potential regulatory network with SASEs of splicing factors and other genes was constructed, which might be part of the biological mechanisms associated with prognosis of BLCA patients. Conclusions: In this study, prognostic signatures constructed using splicing events could be used for predicting the prognosis of BLCA patients.

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