scholarly journals A Computational Analysis of Alternative Splicing across Mammalian Tissues Reveals Circadian and Ultradian Rhythms in Splicing Events

2019 ◽  
Vol 20 (16) ◽  
pp. 3977 ◽  
Author(s):  
Rukeia El-Athman ◽  
Dora Knezevic ◽  
Luise Fuhr ◽  
Angela Relógio
Keyword(s):  
Alternative Splicing ◽  
Circadian Clock ◽  
Computational Analysis ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Expression Patterns ◽  
Rna Seq ◽  
Ultradian Rhythms ◽  
Mammalian Tissues

Mounting evidence points to a role of the circadian clock in the temporal regulation of post-transcriptional processes in mammals, including alternative splicing (AS). In this study, we carried out a computational analysis of circadian and ultradian rhythms on the transcriptome level to characterise the landscape of rhythmic AS events in published datasets covering 76 tissues from mouse and olive baboon. Splicing-related genes with 24-h rhythmic expression patterns showed a bimodal distribution of peak phases across tissues and species, indicating that they might be controlled by the circadian clock. On the output level, we identified putative oscillating AS events in murine microarray data and pairs of differentially rhythmic splice isoforms of the same gene in baboon RNA-seq data that peaked at opposing times of the day and included oncogenes and tumour suppressors. We further explored these findings using a new circadian RNA-seq dataset of human colorectal cancer cell lines. Rhythmic isoform expression patterns differed between the primary tumour and the metastatic cell line and were associated with cancer-related biological processes, indicating a functional role of rhythmic AS that might be implicated in tumour progression. Our data shows that rhythmic AS events are widespread across mammalian tissues and might contribute to a temporal diversification of the proteome.

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 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 Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLU

2020 ◽  
Vol 21 (19) ◽  
pp. 7079
Author(s):  
Seonggyun Han ◽  
Kwangsik Nho ◽  
Younghee Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Alternative Splicing ◽  
Genetic Variants ◽  
Temporal Cortex ◽  
Integrative Approach ◽  
Splicing Regulation ◽  
Rna Seq ◽  
Risk Variant

Clusterin (CLU) is one of the risk genes most associated with late onset Alzheimer’s disease (AD), and several genetic variants in CLU are associated with AD risk. However, the functional role of known AD risk genetic variants in CLU has been little explored. We investigated the effect of an AD risk variant (rs7982) in the 5th exon of CLU on alternative splicing by using an integrative approach of brain-tissue-based RNA-Seq and whole genome sequencing data from Accelerating Medicines Partnership—Alzheimer’s Disease (AMP-AD). RNA-Seq data were generated from three regions in the temporal lobe of the brain—the temporal cortex, superior temporal gyrus, and parahippocampal gyrus. The rs7982 was significantly associated with intron retention (IR) of the 5th exon of CLU; as the number of alternative alleles (G) increased, the IR rates decreased more significantly in females than in males. Our results suggest a sex-dependent role of rs7982 in AD pathogenesis via splicing regulation.

scholarly journals The role of NDRG1 in the pathology and potential treatment of human cancers

2013 ◽  
Vol 66 (11) ◽  
pp. 911-917 ◽  
Author(s):  
Dong-Hun Bae ◽  
Patric J Jansson ◽  
Michael L Huang ◽  
Zaklina Kovacevic ◽  
Danuta Kalinowski ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Anticancer Agents ◽  
Tumour Progression ◽  
Antitumour Activity ◽  
Primary Tumour ◽  
Normal Tissues ◽  
Human Cancers ◽  
Physiological Processes ◽  
Cancer Pathology

N-myc downstream regulated gene 1 (NDRG1) has been well characterised to act as a metastatic suppressor in a number of human cancers. It has also been implicated to have a significant function in a number of physiological processes such as cellular differentiation and cell cycle. In this review, we discuss the role of NDRG1 in cancer pathology. NDRG1 was observed to be downregulated in the majority of cancers. Moreover, the expression of NDRG1 was found to be significantly lower in neoplastic tissues as compared with normal tissues. The most important function of NDRG1 in inhibiting tumour progression is associated with its ability to suppress metastasis. However, it has also been shown to have important effects on other stages of cancer progression (primary tumour growth and angiogenesis). Recently, novel iron chelators with selective antitumour activity (ie, Dp44mT, DpC) were shown to upregulate NDRG1 in cancer cells. Moreover, Dp44mT showed its antimetastatic potential only in cells expressing NDRG1, making this protein an important therapeutic target for cancer chemotherapy. This observation has led to increased interest in the examination of these novel anticancer agents.

scholarly journals Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 188 ◽  
Author(s):  
Liliana Florea ◽  
Li Song ◽  
Steven L Salzberg
Keyword(s):  
Alternative Splicing ◽  
Gene Diversity ◽  
Exon Skipping ◽  
Human Tissues ◽  
Rna Seq ◽  
Gene Splicing ◽  
Link Type ◽  
Normal Human ◽  
Splicing Patterns

Alternative splicing is widely recognized for its roles in regulating genes and creating gene diversity. However, despite many efforts, the repertoire of gene splicing variation is still incompletely characterized, even in humans. Here we describe a new computational system, ASprofile, and its application to RNA-seq data from Illumina’s Human Body Map project (>2.5 billion reads).  Using the system, we identified putative alternative splicing events in 16 different human tissues, which provide a dynamic picture of splicing variation across the tissues. We detected 26,989 potential exon skipping events representing differences in splicing patterns among the tissues. A large proportion of the events (>60%) were novel, involving new exons (~3000), new introns (~16000), or both. When tracing these events across the sixteen tissues, only a small number (4-7%) appeared to be differentially expressed (‘switched’) between two tissues, while 30-45% showed little variation, and the remaining 50-65% were not present in one or both tissues compared.  Novel exon skipping events appeared to be slightly less variable than known events, but were more tissue-specific. Our study represents the first effort to build a comprehensive catalog of alternative splicing in normal human tissues from RNA-seq data, while providing insights into the role of alternative splicing in shaping tissue transcriptome differences. The catalog of events and the ASprofile software are freely available from the Zenodo repository(http://zenodo.org/record/7068; doi:10.5281/zenodo.7068) and from our web site http://ccb.jhu.edu/software/ASprofile.

scholarly journals RNA-Seq analysis in mutant zebrafish reveals role of U1C protein in alternative splicing regulation

2011 ◽  
Vol 30 (10) ◽  
pp. 1965-1976 ◽  
Author(s):  
Tanja Dorothe Rösel ◽  
Lee-Hsueh Hung ◽  
Jan Medenbach ◽  
Katrin Donde ◽  
Stefan Starke ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Splicing Regulation ◽  
Rna Seq

scholarly journals Global Analysis of Circadian Expression in the Cyanobacterium Synechocystis sp. Strain PCC 6803

2005 ◽  
Vol 187 (6) ◽  
pp. 2190-2199 ◽  
Author(s):  
Ken-ichi Kucho ◽  
Kazuhisa Okamoto ◽  
Yuka Tsuchiya ◽  
Satoshi Nomura ◽  
Mamoru Nango ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Dna Microarrays ◽  
Global Analysis ◽  
Bacterial Species ◽  
Physiological State ◽  
Expression Patterns ◽  
Main Role ◽  
Circadian Expression ◽  
Pcc 6803

ABSTRACT Cyanobacteria are the only bacterial species found to have a circadian clock. We used DNA microarrays to examine circadian expression patterns in the cyanobacterium Synechocystis sp. strain PCC 6803. Our analysis identified 54 (2%) and 237 (9%) genes that exhibited circadian rhythms under stringent and relaxed filtering conditions, respectively. The expression of most cycling genes peaked around the time of transition from subjective day to night, suggesting that the main role of the circadian clock in Synechocystis is to adjust the physiological state of the cell to the upcoming night environment. There were several chromosomal regions where neighboring genes were expressed with similar circadian patterns. The physiological functions of the cycling genes were diverse and included a wide variety of metabolic pathways, membrane transport, and signal transduction. Genes involved in respiration and poly(3-hydroxyalkanoate) synthesis showed coordinated circadian expression, suggesting that the regulation is important for the supply of energy and carbon source in the night. Genes involved in transcription and translation also followed circadian cycling patterns. These genes may be important for output of the rhythmic information generated by the circadian clock. Our findings provided critical insights into the importance of the circadian clock on cellular physiology and the mechanism of clock-controlled gene regulation.

A Comprehensive Map of mRNAs and Their Isoforms across All 14 Renal Tubule Segments of Mouse

2021 ◽  
pp. ASN.2020101406
Author(s):  
Lihe Chen ◽  
Chun-Lin Chou ◽  
Mark A. Knepper
Keyword(s):  
Alternative Splicing ◽  
Renal Tubule ◽  
Expression Patterns ◽  
Small Sample ◽  
Full Length ◽  
Renal Physiology ◽  
Regulation Of Transcription ◽  
Rna Seq ◽  
Specific Distribution ◽  
Online Resource

BackgroundThe repertoire of protein expression along the renal tubule depends both on regulation of transcription and regulation of alternative splicing that can generate multiple proteins from a single gene.MethodsA full-length, small-sample RNA-seq protocol profiled transcriptomes for all 14 renal tubule segments microdissected from mouse kidneys.ResultsThis study identified >34,000 transcripts, including 3709 that were expressed in a segment-specific manner. All data are provided as an online resource (https://esbl.nhlbi.nih.gov/MRECA/Nephron/). Many of the genes expressed in unique patterns along the renal tubule were solute carriers, transcription factors, or G protein–coupled receptors that account for segment-specific function. Mapping the distribution of transcripts associated with Wnk-SPAK-PKA signaling, renin-angiotensin-aldosterone signaling, and cystic diseases of the kidney illustrated the applications of the online resource. The method allowed full-length mapping of RNA-seq reads, which facilitated comprehensive, unbiased characterization of alternative exon usage along the renal tubule, including known isoforms of Cldn10, Kcnj1 (ROMK), Slc12a1 (NKCC2), Wnk1, Stk39 (SPAK), and Slc14a2 (UT-A urea transporter). It also identified many novel isoforms with segment-specific distribution. These included variants associated with altered protein structure (Slc9a8, Khk, Tsc22d1, and Scoc), and variants that may affect untranslated, regulatory regions of transcripts (Pth1r, Pkar1a, and Dab2).ConclusionsFull-length, unbiased sequencing of transcripts identified gene-expression patterns along the mouse renal tubule. The data, provided as an online resource, include both quantitative and qualitative differences in transcripts. Identification of alternative splicing along the renal tubule may prove critical to understanding renal physiology and pathophysiology.

scholarly journals Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 188 ◽  
Author(s):  
Liliana Florea ◽  
Li Song ◽  
Steven L Salzberg
Keyword(s):  
Alternative Splicing ◽  
Gene Diversity ◽  
Exon Skipping ◽  
Human Tissues ◽  
Rna Seq ◽  
Gene Splicing ◽  
Link Type ◽  
Normal Human ◽  
Splicing Patterns

Alternative splicing is widely recognized for its roles in regulating genes and creating gene diversity. However, despite many efforts, the repertoire of gene splicing variation is still incompletely characterized, even in humans. Here we describe a new computational system, ASprofile, and its application to RNA-seq data from Illumina’s Human Body Map project (>2.5 billion reads).  Using the system, we identified putative alternative splicing events in 16 different human tissues, which provide a dynamic picture of splicing variation across the tissues. We detected 26,989 potential exon skipping events representing differences in splicing patterns among the tissues. A large proportion of the events (>60%) were novel, involving new exons (~3000), new introns (~16000), or both. When tracing these events across the sixteen tissues, only a small number (4-7%) appeared to be differentially expressed (‘switched’) between two tissues, while 30-45% showed little variation, and the remaining 50-65% were not present in one or both tissues compared.  Novel exon skipping events appeared to be slightly less variable than known events, but were more tissue-specific. Our study represents the first effort to build a comprehensive catalog of alternative splicing in normal human tissues from RNA-seq data, while providing insights into the role of alternative splicing in shaping tissue transcriptome differences. The catalog of events and the ASprofile software are freely available from the Zenodo repository(http://zenodo.org/record/7068; doi:10.5281/zenodo.7068) and from our web site http://ccb.jhu.edu/software/ASprofile.

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

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