Variation in alternative splicing across human tissues

BackgroundAlternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues.ResultsControlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were about 50 to 100% higher in the liver than in any other human tissue studied. Quantifying differences in splice junction usage, the brain, pancreas, liver and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-arginine protein and heterogeneous ribonucleoprotein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in liver. Sequence motifs enriched in alternative exons in genes expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues.ConclusionsThis study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-acting factors likely to have important roles in tissue-specific AS in human cells.

• Publication year

  2004

• Venue

  Genome Biology

• Publication date

  2004-09-13

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/gb-2004-5-10-r74PMID 15461793PMCID 545594
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Primer of Biostatistics: Sixth Edition

  2005cited by this paper
• In NF1, CFTR, PER3, CARS and SYT7, alternatively included exons show higher conservation of surrounding intron sequences than constitutive exons

  2004cited by this paper
• An unappreciated role for RNA surveillance

  2004cited by this paper
• Autoregulation of polypyrimidine tract binding protein by alternative splicing leading to nonsense-mediated decay.

  2004cited by this paper
• A gene atlas of the mouse and human protein-encoding transcriptomes.

  2004influential reference
• Identification of alternatively spliced mRNA variants related to cancers by genome-wide ESTs alignment

  2004cited by this paper
• Positional clustering of differentially expressed genes on human chromosomes 20, 21 and 22

  2003cited by this paper
• Genome-Wide Survey of Human Alternative Pre-mRNA Splicing with Exon Junction Microarrays

  2003cited by this paper
• Impact of alternative initiation, splicing, and termination on the diversity of the mRNA transcripts encoded by the mouse transcriptome.

  2003cited by this paper
• Pre-mRNA splicing: awash in a sea of proteins.

  2003cited by this paper
• Widespread predicted nonsense-mediated mRNA decay of alternatively-spliced transcripts of human normal and disease genes

  2003cited by this paper
• Computational analysis and experimental validation of tumor-associated alternative RNA splicing in human cancer.

  2003cited by this paper
• Intronic sequences flanking alternatively spliced exons are conserved between human and mouse.

  2003cited by this paper
• Transcriptome and Genome Conservation of Alternative Splicing Events in Humans and Mice

  2003cited by this paper
• Pre-mRNA splicing and human disease.

  2003cited by this paper
• Alternative splicing in the nervous system: an emerging source of diversity and regulation.

  2003cited by this paper
• Is prokaryotic complexity limited by accelerated growth inregulatory overhead?

  2003cited by this paper
• Mechanisms of alternative pre-messenger RNA splicing.

  2003cited by this paper
• CLIP Identifies Nova-Regulated RNA Networks in the Brain

  2003cited by this paper
• Single Molecule Profiling of Alternative Pre-mRNA Splicing

  2003cited by this paper
• Distribution and characterization of regulatory elements in the human genome.

  2002cited by this paper
• Large-scale proteomic analysis of the human spliceosome.

  2002cited by this paper
• Alternative splicing and genome complexity

  2002cited by this paper
• Comprehensive proteomic analysis of the human spliceosome

  2002cited by this paper
• Categorization and characterization of transcript-confirmed constitutively and alternatively spliced introns and exons from human.

  2002cited by this paper
• CD44 in Cancer

  2002cited by this paper
• Predictive Identification of Exonic Splicing Enhancers in Human Genes

  2002cited by this paper
• SR proteins and hnRNP H regulate the splicing of the HIV‐1 tev‐specific exon 6D

  2002cited by this paper
• Genome-wide detection of tissue-specific alternative splicing in the human transcriptome.

  2002cited by this paper
• Selecting for functional alternative splices in ESTs.

  2002cited by this paper
• Large-scale analysis of the human and mouse transcriptomes

  2002influential reference
• Listening to silence and understanding nonsense: exonic mutations that affect splicing

  2002cited by this paper
• Genomewide Analysis of mRNA Processing in Yeast Using Splicing-Specific Microarrays

  2002cited by this paper
• Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae*S

  2002cited by this paper
• A genomic view of alternative splicing

  2002cited by this paper
• Strong RNA Splicing Enhancers Identified by a Modified Method of Cycled Selection Interact with SR Protein*

  2001cited by this paper
• Genome-wide detection of alternative splicing in expressed sequences of human genes

  2001cited by this paper
• Computational analysis of candidate intron regulatory elements for tissue-specific alternative pre-mRNA splicing.

  2001cited by this paper
• A computational analysis of sequence features involved in recognition of short introns

  2001cited by this paper
• The CELF Family of RNA Binding Proteins Is Implicated in Cell-Specific and Developmentally Regulated Alternative Splicing

  2001cited by this paper
• Comparative genomic sequence analysis of the FXR gene family: FMR1, FXR1, and FXR2.

  2001cited by this paper
• Alternative splicing: increasing diversity in the proteomic world.

  2001cited by this paper
• Predicting splice variant from DNA chip expression data.

  2001cited by this paper
• Selection of Alternative 5′ Splice Sites: Role of U1 snRNP and Models for the Antagonistic Effects of SF2/ASF and hnRNP A1

  2000cited by this paper
• EST comparison indicates 38% of human mRNAs contain possible alternative splice forms

  2000cited by this paper
• Genetic evidence for a Nova regulator of alternative splicing in the brain.

  2000cited by this paper
• Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability.

  2000cited by this paper
• Multisite RNA binding and release of polypyrimidine tract binding protein during the regulation of c-src neural-specific splicing.

  2000cited by this paper
• An Alternative-Exon Database and Its Statistical Analysis

  2000influential reference
• hnRNP A/B proteins are required for inhibition of HIV‐1 pre‐mRNA splicing

  1999cited by this paper
• Selection and Characterization of Pre-mRNA Splicing Enhancers: Identification of Novel SR Protein-Specific Enhancer Sequences

  1999cited by this paper
• Control of 3' splice site choice in vivo by ASF/SF2 and hnRNP A1.

  1999cited by this paper
• Frequent alternative splicing of human genes.

  1999cited by this paper
• A Sampling of the Yeast Proteome

  1999cited by this paper
• Alternative splicing in the murine and human FXR1 genes.

  1999cited by this paper
• Regulated tissue-specific expression of antagonistic pre-mRNA splicing factors.

  1998cited by this paper
• Alternative splicing of pre-mRNA: developmental consequences and mechanisms of regulation.

  1998cited by this paper
• A computer program for aligning a cDNA sequence with a genomic DNA sequence.

  1998influential reference
• Splicing regulation in neurons: tinkering with cell-specific control.

  1998cited by this paper
• Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins.

  1998cited by this paper
• The polypyrimidine tract binding protein binds upstream of neural cell-specific c-src exon N1 to repress the splicing of the intron downstream

  1997cited by this paper
• A comparison of selected mRNA and protein abundances in human liver

  1997cited by this paper
• A complex intronic splicing enhancer from the c-src pre-mRNA activates inclusion of a heterologous exon

  1997cited by this paper
• G triplets located throughout a class of small vertebrate introns enforce intron borders and regulate splice site selection

  1997cited by this paper
• Expression profiles of active genes in human and mouse livers.

  1996cited by this paper
• Cell type-specific expression of hnRNP proteins.

  1995cited by this paper
• The developmental consequences of alternate splicing in sex determination and differentiation in Drosophila.

  1995cited by this paper
• An intronic (A/U)GGG repeat enhances the splicing of an alternative intron of the chicken beta-tropomyosin pre-mRNA.

  1995cited by this paper
• Exon Recognition in Vertebrate Splicing (*)

  1995cited by this paper
• RNA binding specificity of hnRNP A1: significance of hnRNP A1 high‐affinity binding sites in pre‐mRNA splicing.

  1994cited by this paper
• Primer of biostatistics : statistical software program version 6.0

  1981cited by this paper
• Predictive Identification of Exonic Splicing Enhancers in Human Genes

  year unknowncited by this paper

• Decoding exon inclusion in the human brain reveals more divergent splicing mechanisms in neurons than glia.

  2026cites this paper
• Allele-specific splicing modulates protein isoforms and Alzheimer’s risk

  2026cites this paper
• HDAC Inhibition Reshapes Splicing of Synaptic Plasticity-Related Genes and Neural Network Dynamics

  2026cites this paper
• Stochastic Nanoscale Biophysical Cues as a Basis for the Induction of Glioblastoma-Like Transcriptional Programs in Astrocytes.

  2026cites this paper
• Single-cell and isoform-specific translational profiling of the mouse brain.

  2026cites this paper
• Neural microexons contain lengthened sequence and extended RNA structure between the branchpoint and splice site motif

  2026influential citation
• Pregnancy induces extensive changes of transcript usage in the goat brain.

  2025cites this paper
• ‘The bud disappears when the blossom breaks through’: composing dialectical lectures as environmental education

  2025cites this paper
• Classification and Quantification of Unproductive Splicing Events

  2025cites this paper
• Dynamic changes in mRNA isoform usage during human retinal development

  2025cites this paper
• A role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration

  2025cites this paper
• Endothelial Adgrl2 expression and alternative splicing controls the cerebrovasculature

  2025cites this paper
• Single cell and spatial alternative splicing analysis with Nanopore long read sequencing

  2025cites this paper
• SRSF12 is a primate-specific splicing factor that induces a tissue-specific gene expression program

  2025cites this paper
• A novel conditional knock-in mouse model for APOE4-to-APOE3 switching.

  2025cites this paper
• Reverse engineering neuron-type-specific and type-orthogonal splicing-regulatory networks using diverse cellular transcriptomes

  2025cites this paper
• Synergy between RNA editing and alternative splicing modulates the biological properties of the voltage-gated calcium channel CaV1.3

  2025cites this paper
• DOLPHIN advances single-cell transcriptomics beyond gene level by leveraging exon and junction reads

  2025cites this paper
• Neuron-specific repression of alternative splicing by the conserved CELF protein UNC-75 in Caenorhabditis elegans

  2025cites this paper
• EML2 and EML4 splice variants regulate microtubule remodeling during neuronal cell differentiation

  2025cites this paper
• Exon-variant interplay and multi-modal evidence identify endocrine dysregulation in severe psychiatric disorders impacting excitatory neurons

  2025influential citation
• Pluripotent stem cells-based neural organoids for modelling human brain development and diseases

  2025cites this paper
• The Role of mRNA Alternative Processing in Mammalian Neurodevelopment

  2025cites this paper
• Alternative splicing across the C. elegans nervous system

  2025cites this paper
• Cryptic splicing in synaptic and membrane excitability genes links TDP-43 loss to neuronal dysfunction

  2025cites this paper
• RNA-seq Splicing Profile of the CDH1 Gene and Its Impact on the Clinical Pathogenicity Classification of CDH1 Variants: A Description of Alternative and Pathogenic Splicing Patterns

  2025cites this paper
• Functional analysis of a novel segment deletion in the FRMD7 gene causing X-linked idiopathic congenital nystagmus.

  2025cites this paper
• Human Kidney Alternative Splicing Information Illuminates Cardiovascular-Kidney-Metabolic Syndrome Risk

  2025cites this paper
• A role for the spinal cord cholinergic neuron circadian clock in RNA metabolism and mediating ALS disease phenotypes

  2025cites this paper
• Coordinated neuron-specific splicing events restrict nucleosome engagement of the LSD1 histone demethylase complex

  2025cites this paper
• Loss of full-length DAZL isoform disrupts PABPC1-dependent translational regulation and meiosis

  2025cites this paper
• Genomic and Transcriptomic Analysis of Ninein Alternative Splicing Between C57BL/6J and DBA/2J Mice

  2024cites this paper
• Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms

  2024cites this paper
• MBL-1/Muscleblind regulates neuronal differentiation and controls the splicing of a terminal selector in Caenorhabditis elegans

  2024cites this paper
• The role of HnrnpF/H as a driver of oligoteratozoospermia

  2024cites this paper
• Non-coding RNA contribution to aging and lifespan.

  2024cites this paper
• Predicting cell-type-specific exon inclusion in the human brain reveals more complex splicing mechanisms in neurons than glia

  2024cites this paper
• Complete characterization of the yak testicular development using accurate full-length transcriptome sequencing.

  2024cites this paper
• Uncovering a multitude of stage-specific splice variants and putative protein isoforms generated along mouse spermatogenesis

  2024cites this paper
• Regulation of DNA Damage Response by RNA/DNA-Binding Proteins: Implications for Neurological Disorders and Aging.

  2024cites this paper
• Ninein, a candidate gene for ethanol anxiolysis, shows complex exon-specific expression and alternative splicing differences between C57BL/6J and DBA/2J mice

  2024cites this paper
• Post-transcriptional regulation of the transcriptional apparatus in neuronal development

  2024cites this paper
• Reverse engineering neuron type-specific and type-orthogonal splicing-regulatory networks using single-cell transcriptomes

  2024cites this paper
• A novel human protein-coding locus identified using a targeted RNA enrichment technique

  2024cites this paper
• Predicting splicing patterns from the transcription factor binding sites in the promoter with deep learning

  2024cites this paper
• Differential Analysis of Alternative Splicing Events in gene regions using Residual Neural Networks

  2024cites this paper
• Characterization of alternative splicing during mammalian brain development reveals the extent of isoform diversity and potential effects on protein structural changes

  2024cites this paper
• CPSF4-mediated regulation of alternative splicing of HMG20B facilitates the progression of triple-negative breast cancer

  2024cites this paper
• Bioinformatics-driven refinement of the commonly used TPI nonsense-mediated decay reporter system

  2024cites this paper
• RNA in axons, dendrites, synapses and beyond

  2024cites this paper
• Transcriptomics : Approaches to Quantifying Gene Expression and Their Application to Studying the Human Brain.

  2024cites this paper
• APOER2 splicing repertoire in Alzheimer’s disease: Insights from long-read RNA sequencing

  2024cites this paper
• Long-read sequencing reveals the RNA isoform repertoire of neuropsychiatric risk genes in human brain

  2024cites this paper
• TREX tetramer disruption alters RNA processing necessary for corticogenesis in THOC6 Intellectual Disability Syndrome

  2024cites this paper
• SRSF2 safeguards efficient transcription of DNA damage and repair genes.

  2024cites this paper
• Disruption of nuclear speckle integrity dysregulates RNA splicing in C9ORF72-FTD/ALS.

  2024cites this paper
• MRI tractographic validation of drug-enhanced hepatic clearance of amyloid-beta and the therapeutic potential for Alzheimer's Disease: A Pilot Study.

  2024cites this paper
• Splicing to orchestrate cell fate

  2024cites this paper
• Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids

  2023cites this paper
• Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease

  2023cites this paper
• The Roles of hnRNP Family in the Brain and Brain-Related Disorders

  2023cites this paper
• Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review

  2023cites this paper
• Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease

  2023cites this paper
• Single cell and spatial alternative splicing analysis with long read sequencing

  2023cites this paper
• Hidden Genetic Regulation of Human Complex Traits via Brain Isoforms

  2023cites this paper
• Alternative splicing impacts microRNA regulation within coding regions

  2023cites this paper
• MAEL gene contributes to bovine testicular development through the m5C-mediated splicing

  2023cites this paper
• Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington's disease

  2023cites this paper
• Intron retention of an adhesion GPCR generates single transmembrane-helix isoforms to enable 7TM-adhesion GPCR function

  2023cites this paper
• Specific expression of alternatively spliced genes in the turkey (Meleagris gallopavo) reproductive tract revealed their function in spermatogenesis and post-testicular sperm maturation

  2023cites this paper
• Multiple Sgip1 Splice Variants Inhibit Cannabinoid Receptor 1 Internalization.

  2023cites this paper
• Alternative splicing is not a key source of chemerin isoforms diversity

  2023cites this paper
• Characterization of Alternative Splicing During Mammalian Brain Development Reveals the Magnitude of Isoform Diversity and its Effects on Protein Conformational Changes

  2023cites this paper
• Biophysical basis for the induction of glioblastoma-like phenotype in astrocytes

  2023cites this paper
• RBFOX2 regulated EYA3 isoforms partner with SIX4 or ZBTB1 to control transcription during myogenesis

  2023cites this paper
• Alternative RNA Splicing in the Retina: Insights and Perspectives.

  2023cites this paper
• Splitpea: quantifying protein interaction network rewiring changes due to alternative splicing in cancer

  2023cites this paper
• Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects

  2023cites this paper
• Alternative splicing in neurodegenerative disease and the promise of RNA therapies

  2023cites this paper
• Predicting splicing patterns from the transcription factor binding sites in the promoter with deep learning

  2023cites this paper
• Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington’s disease

  2023cites this paper
• RNA alternative splicing impacts the risk for alcohol use disorder

  2023cites this paper
• Tissue-specific regulation of gene expression via unproductive splicing

  2023cites this paper
• Functional Characterisation of the Circular RNA, circHTT(2-6), in Huntington’s Disease

  2023cites this paper
• Identification of Alternative Splicing in Proteomes of Human Melanoma Cell Lines without RNA Sequencing Data

  2023cites this paper
• Alternative splicing of CEACAM1 by hypoxia-inducible factor–1α enhances tolerance to hepatic ischemia in mice and humans

  2023cites this paper
• A neuron-specific microexon ablates the novel DNA-binding function of a histone H3K4me0 reader PHF21A

  2023cites this paper
• Alternative splicing shapes the transcriptome complexity in blackgram [Vigna mungo (L.) Hepper]

  2023cites this paper
• Deciphering RNA splicing logic with interpretable machine learning

  2023cites this paper
• SRSF10 is essential for progenitor spermatogonia expansion by regulating alternative splicing

  2022cites this paper
• Bioinformatics detection of modulators controlling splicing factor‐dependent intron retention in the human brain

  2022cites this paper
• Predicting exon criticality from protein sequence

  2022cites this paper
• Tau‐induced deficits in nonsense‐mediated mRNA decay contribute to neurodegeneration

  2022cites this paper
• LAFITE Reveals the Complexity of Transcript Isoforms in Subcellular Fractions

  2022cites this paper
• Cell-type-specific alternative splicing in the Arabidopsis germline

  2022cites this paper
• Machine learning for discovery: deciphering RNA splicing logic

  2022cites this paper
• Posttranscriptional regulation of neurofilament proteins and tau in health and disease

  2022cites this paper
• Proteomic Analysis of Adult Human Hippocampal Subfields Demonstrates Regional Heterogeneity in the Protein Expression.

  2022cites this paper
• Prediction of transcript isoforms in 19 chicken tissues by Oxford Nanopore long-read sequencing

  2022cites this paper
• The alternative proteome in neurobiology

  2022cites this paper