Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu's unique role in shaping the human transcriptome

BackgroundTransposed elements (TEs) have a substantial impact on mammalian evolution and are involved in numerous genetic diseases. We compared the impact of TEs on the human transcriptome and the mouse transcriptome.ResultsWe compiled a dataset of all TEs in the human and mouse genomes, identifying 3,932,058 and 3,122,416 TEs, respectively. We than extracted TEs located within human and mouse genes and, surprisingly, we found that 60% of TEs in both human and mouse are located in intronic sequences, even though introns comprise only 24% of the human genome. All TE families in both human and mouse can exonize. TE families that are shared between human and mouse exhibit the same percentage of TE exonization in the two species, but the exonization level of Alu, a primate-specific retroelement, is significantly greater than that of other TEs within the human genome, leading to a higher level of TE exonization in human than in mouse (1,824 exons compared with 506 exons, respectively). We detected a primate-specific mechanism for intron gain, in which Alu insertion into an exon creates a new intron located in the 3' untranslated region (termed 'intronization'). Finally, the insertion of TEs into the first and last exons of a gene is more frequent in human than in mouse, leading to longer exons in human.ConclusionOur findings reveal many effects of TEs on these two transcriptomes. These effects are substantially greater in human than in mouse, which is due to the presence of Alu elements in human.

• Publication year

  2007

• Venue

  Genome Biology

• Publication date

  2007-06-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/gb-2007-8-6-r127arXiv 0811.3510PMID 17594509PMCID 2394776
• 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.

• RNA-editing-mediated exon evolution

  2007influential reference
• The evolutionary history of human DNA transposons: evidence for intense activity in the primate lineage.

  2007cited by this paper
• Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs.

  2007cited by this paper
• Evolutionary history of 7SL RNA-derived SINEs in Supraprimates.

  2007cited by this paper
• Modern origin of numerous alternatively spliced human introns from tandem arrays

  2007cited by this paper
• Phylogeny of Phagotrophic Euglenids (Euglenozoa) as Inferred from Hsp90 Gene Sequences

  2007cited by this paper
• Regulation of gene expression by alternative untranslated regions.

  2006cited by this paper
• Alternative splicing and RNA selection pressure — evolutionary consequences for eukaryotic genomes

  2006cited by this paper
• Gene function and expression level influence the insertion/fixation dynamics of distinct transposon families in mammalian introns

  2006cited by this paper
• A distal enhancer and an ultraconserved exon are derived from a novel retroposon

  2006influential reference
• Alu elements as regulators of gene expression

  2006cited by this paper
• Transcription factor YY1: structure, function, and therapeutic implications in cancer biology

  2006cited by this paper
• Characterization of intron loss events in mammals.

  2006cited by this paper
• Do transposable elements really contribute to proteomes?

  2006influential reference
• Genomic splice-site analysis reveals frequent alternative splicing close to the dominant splice site.

  2006cited by this paper
• Long L1 insertions in human gene introns specifically reduce the content of corresponding primary transcripts

  2006cited by this paper
• Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression.

  2006cited by this paper
• Comparison of multiple vertebrate genomes reveals the birth and evolution of human exons

  2006influential reference
• Disparity, adaptation, exaptation, bookkeeping, and contingency at the genome level

  2005cited by this paper
• The importance of being divisible by three in alternative splicing

  2005cited by this paper
• Origin and evolution of new exons in rodents.

  2005cited by this paper
• uAUG and uORFs in human and rodent 5'untranslated mRNAs.

  2005cited by this paper
• Identification of Splicing Silencers and Enhancers in Sense Alus: a Role for Pseudoacceptors in Splice Site Repression

  2005cited by this paper
• Alu-SINE exonization: en route to protein-coding function.

  2005cited by this paper
• The PROSITE database

  2005influential reference
• Fixation of conserved sequences shapes human intron size and influences transposon-insertion dynamics.

  2005cited by this paper
• A systematic analysis of LINE-1 endonuclease-dependent retrotranspositional events causing human genetic disease

  2005cited by this paper
• LINE‐1 retrotransposons: Modulators of quantity and quality of mammalian gene expression?

  2005cited by this paper
• Database resources of the National Center for Biotechnology Information

  2005cited by this paper
• From the margins of the genome: mobile elements shape primate evolution

  2005cited by this paper
• How did alternative splicing evolve?

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

  2004cited by this paper
• Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes

  2004cited by this paper
• The origin of recent introns: transposons?

  2004cited by this paper
• Evidence for a subpopulation of conserved alternative splicing events under selection pressure for protein reading frame preservation.

  2004cited by this paper
• Minimal conditions for exonization of intronic sequences: 5' splice site formation in alu exons.

  2004influential reference
• How prevalent is functional alternative splicing in the human genome?

  2004cited by this paper
• YY1AP, A Novel Co-activator of YY1*

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

  2004cited by this paper
• Mobile elements and mammalian genome evolution.

  2003cited by this paper
• Discovery of novel splice forms and functional analysis of cancer-specific alternative splicing in human expressed sequences.

  2003cited by this paper
• Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss

  2003cited by this paper
• The Birth of an Alternatively Spliced Exon: 3' Splice-Site Selection in Alu Exons

  2003influential reference
• Computational analysis and experimental validation of tumor-associated alternative RNA splicing in human cancer.

  2003cited by this paper
• Large-scale comparison of intron positions in mammalian genes shows intron loss but no gain

  2003cited by this paper
• Initial sequencing and comparative analysis of the mouse genome

  2002cited by this paper
• Alternative Splicing of the Adenylyl Cyclase Stimulatory G-protein Gαs Is Regulated by SF2/ASF and Heterogeneous Nuclear Ribonucleoprotein A1 (hnRNPA1) and Involves the Use of an Unusual TG 3′-Splice Site*

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

  2002cited by this paper
• Alu-containing exons are alternatively spliced.

  2002cited by this paper
• Initial sequencing and analysis of the human genome

  2001influential reference
• KUB3 amplification and overexpression in human gliomas

  2001cited by this paper
• Repbase update: a database and an electronic journal of repetitive elements.

  2000cited by this paper
• RepeatMasker

  2000cited by this paper
• A novel Alu-like element rearranged in the dystrophin gene causes a splicing mutation in a family with X-linked dilated cardiomyopathy.

  1998cited by this paper
• Evolutionary relationship of plant catalase genes inferred from exon-intron structures: isozyme divergence after the separation of monocots and dicots

  1998cited by this paper
• Functional analysis of the polypyrimidine tract in pre-mRNA splicing.

  1997cited by this paper
• Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette.

  1997cited by this paper
• On "genomenclature": a comprehensive (and respectful) taxonomy for pseudogenes and other "junk DNA".

  1992cited by this paper

• The role of transposable elements activity in genomic instability and their relationship to aging process.

  2026cites this paper
• Cryptic Last Exon splicing is a conserved tuning mechanism during neural development

  2026cites this paper
• Comparative genomic and transcriptome analyses of transposable elements in buffalo identify key short interspersed element-derived genes for testicular and muscle development.

  2025cites this paper
• Analysis of a Novel Human Protein, ORF3, Encoded by Spacer rDNA

  2025cites this paper
• ADAR1 editing is necessary for only a small subset of cytosolic dsRNAs to evade MDA5-mediated autoimmunity

  2025cites this paper
• Reactivation of retrotransposable elements is associated with environmental stress and ageing

  2025cites this paper
• The mRNA export pathway licenses viral mimicry response and antitumor immunity by actively exporting nuclear retroelement transcripts.

  2025cites this paper
• Transposon-host arms race: a saga of genome evolution.

  2025cites this paper
• Viral mimicry in cancer therapy.

  2025cites this paper
• Charting the regulatory landscape of TP53 on transposable elements in cancer

  2025cites this paper
• Transposon-derived introns as an element shaping the structure of eukaryotic genomes

  2024cites this paper
• LINE-1 transposable element renaissance in aging and age-related diseases.

  2024cites this paper
• Autonomous transposons tune their sequences to ensure somatic suppression

  2024cites this paper
• Genomic analyses of intricate interaction of TE-lncRNA overlapping genes with miRNAs in human diseases

  2024cites this paper
• Mechanisms and regulation of spliceosome-mediated pre-mRNA splicing in Saccharomyces cerevisiae

  2024cites this paper
• The Regulation and Immune Signature of Retrotransposons in Cancer

  2023influential citation
• SINE-derived short noncoding RNAs: their evolutionary origins, molecular mechanisms, and physiological significance

  2023cites this paper
• Epigenetically controlled tumor antigens derived from splice junctions between exons and transposable elements

  2023cites this paper
• 4.5SH RNA counteracts deleterious exonization of SINE B1 in mice.

  2023cites this paper
• PARP1 Regulates Circular RNA Biogenesis though Control of Transcriptional Dynamics

  2023cites this paper
• Noncanonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent neo-antigens in patients with lung cancer

  2023cites this paper
• Conserved microRNAs and Flipons Shape Gene Expression during Development by Altering Promoter Conformations

  2023cites this paper
• Alu RNA fold links splicing with signal recognition particle proteins

  2023cites this paper
• Comprehensive In Silico Analysis of Retrotransposon Insertions within the Survival Motor Neuron Genes Involved in Spinal Muscular Atrophy

  2022cites this paper
• ExoPLOT: Representation of alternative splicing in human tissues and developmental stages with transposed element (TE) involvement.

  2022cites this paper
• Adversary of DNA integrity: a long non-coding RNA stimulates driver oncogenic chromosomal rearrangement in human thyroid cells

  2022cites this paper
• Antisense Oligonucleotide Rescue of Deep-Intronic Variants Activating Pseudoexons in the 6-Pyruvoyl-Tetrahydropterin Synthase Gene

  2022cites this paper
• Long-read direct RNA sequencing reveals epigenetic regulation of chimeric gene-transposon transcripts in Arabidopsis thaliana

  2022cites this paper
• The Role of Retroelements in the Evolution of Animal Genomes

  2022cites this paper
• Recent insights into crosstalk between genetic parasites and their host genome

  2022cites this paper
• The Role of Transposable Elements of the Human Genome in Neuronal Function and Pathology

  2022cites this paper
• Meta-Analysis Suggests That Intron Retention Can Affect Quantification of Transposable Elements from RNA-Seq Data

  2022cites this paper
• Distinct composition and amplification dynamics of transposable elements in sacred lotus (Nelumbo nucifera Gaertn.)

  2022cites this paper
• The Role of Retroelements in the Evolution of Animal Genomes

  2022cites this paper
• A Small Subset of Cytosolic dsRNAs Must Be Edited by ADAR1 to Evade MDA5-Mediated Autoimmunity

  2022cites this paper
• Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants

  2022cites this paper
• The Transposable Element Environment of Human Genes Differs According to Their Duplication Status and Essentiality

  2021cites this paper
• The pattern of gene copy number alteration (CNAs) in hepatocellular carcinoma: an in silico analysis

  2021cites this paper
• New exon and accelerated evolution of placental gene Nrk occurred in the ancestral lineage of placental mammals.

  2021cites this paper
• Localization of RNAs in the nucleus: cis- and trans- regulation

  2021cites this paper
• Restriction of an intron size en route to endothermy

  2021cites this paper
• Detection of Alu Exonization Events in Human Frontal Cortex From RNA-Seq Data

  2021cites this paper
• ALU A-to-I RNA Editing: Millions of Sites and Many Open Questions.

  2021cites this paper
• New exon ignites accelerated evolution of placental gene Nrk in the ancestral lineage of eutherians

  2021cites this paper
• Transposable element-derived sequences in vertebrate development

  2021cites this paper
• RNA Editing: Methods and Protocols

  2021cites this paper
• Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer.

  2021cites this paper
• Dynamic Variations of 3′UTR Length Reprogram the mRNA Regulatory Landscape

  2021cites this paper
• An Overview on the Complexity of OCT4: at the Level of DNA, RNA and Protein

  2021cites this paper
• Retroelement-derived RNA and its role in the brain.

  2020cites this paper
• CircRNAs open a new era in the study of cardiovascular disease (Review)

  2020cites this paper
• Genomic Characterization of Human Long Noncoding RNAs

  2020cites this paper
• Transposon clusters as substrates for aberrant splice-site activation

  2020influential citation
• The landscape of accessible chromatin in bovine oocytes and early embryos

  2020cites this paper
• Short interspersed nuclear element (SINE)-mediated post-transcriptional effects on human and mouse gene expression: SINE-UP for active duty

  2020cites this paper
• Transposable elements as a potent source of diverse cis-regulatory sequences in mammalian genomes

  2020cites this paper
• Perspectives on studying molecular adaptations of amphibians in the genomic era

  2020cites this paper
• ALU non-B-DNA conformations, flipons, binary codes and evolution

  2020cites this paper
• The Contribution of Retrotransposons to the Transcriptomes of Murine Somatic Cells

  2019cites this paper
• Comprehensive genomic analysis reveals dynamic evolution of endogenous retroviruses that code for retroviral-like protein domains

  2019cites this paper
• Blood biomarkers in chronic obstructive pulmonary disease (COPD)

  2019cites this paper
• Mechanistic Basis for Control of Early Embryonic Development by a 5’ tRNA Fragment

  2019cites this paper
• Bioinformatic analysis of regulation of natural antisense transcripts by transposable elements in human mRNA.

  2019cites this paper
• Long-read direct RNA sequencing by 5’-Cap capturing reveals the impact of Piwi on the widespread exonization of transposable elements in locusts

  2019cites this paper
• Evolution of the human cold/menthol receptor, TRPM8.

  2019cites this paper
• Impact of polymorphic transposable elements on transcription in lymphoblastoid cell lines from public data

  2019cites this paper
• Rapidly evolving protointrons in Saccharomyces genomes revealed by a hungry spliceosome

  2019cites this paper
• Mouse germ line mutations due to retrotransposon insertions

  2019cites this paper
• Accelerated evolution of toxin genes: Exonization and intronization in snake venom disintegrin/metalloprotease genes

  2018cites this paper
• All I's on the RADAR: role of ADAR in gene regulation

  2018cites this paper
• ALUminating the Path of Atherosclerosis Progression: Chaos Theory Suggests a Role for Alu Repeats in the Development of Atherosclerotic Vascular Disease

  2018cites this paper
• Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay

  2018cites this paper
• Molecular functions and specific roles of circRNAs in the cardiovascular system

  2018cites this paper
• Alu exaptation enriches the human transcriptome by introducing new gene ends

  2018cites this paper
• Reccurrent F8 Intronic Deletion Found in Mild Hemophilia A Causes Alu Exonization.

  2018cites this paper
• RNA Editing and Retrotransposons in Neurology

  2018influential citation
• Epigenetic regulation of intragenic transposable elements: a two-edged sword

  2018cites this paper
• Genome-Wide Analysis of the Association of Transposable Elements with Gene Regulation Suggests that Alu Elements Have the Largest Overall Regulatory Impact

  2018cites this paper
• Hypermethylated LTR retrotransposon exhibits enhancer activity

  2017cites this paper
• The Transcriptional Logic of Mammalian Neuronal Diversity

  2017cites this paper
• Ancient exapted transposable elements drive nuclear localisation of lncRNAs

  2017cites this paper
• The expression and construction of engineering Escherichia coli producing humanized AluY RNAs

  2017cites this paper
• A birth of bipartite exon by intragenic deletion

  2017influential citation
• Characterization of lincRNA expression in the human retinal pigment epithelium and differentiated induced pluripotent stem cells

  2017cites this paper
• Long non-coding RNAs transcribed by ERV-9 LTR retrotransposon act in cis to modulate long-range LTR enhancer function

  2017cites this paper
• Genome-wide analysis of the association of transposable elements with gene regulation suggests that Alu elements have the largest overall regulatory impact

  2017cites this paper
• From intronization to intron loss: How the interplay between mRNA-associated processes can shape the architecture and the expression of eukaryotic genes.

  2017cites this paper
• A protein complex regulates RNA processing of intronic heterochromatin-containing genes in Arabidopsis

  2017cites this paper
• Ancient exapted transposable elements promote nuclear enrichment of human long noncoding RNAs

  2017influential citation
• RNAEditor: easy detection of RNA editing events and the introduction of editing islands

  2016cites this paper
• The contribution of Alu exons to the human proteome

  2016cites this paper
• Expression of evolutionarily novel genes in tumors.

  2016cites this paper
• MIR retroposon exonization promotes evolutionary variability and generates species-specific expression of IGF-1 splice variants.

  2016cites this paper
• Global analyses of endonucleolytic cleavage in mammals reveal expanded repertoires of cleavage-inducing small RNAs and their targets

  2016cites this paper
• A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq

  2016cites this paper
• Expression of evolutionarily novel genes in tumors

  2016cites this paper
• Identification of Alternative Variants and Insertion of the Novel Polymorphic AluYl17 in TSEN54 Gene during Primate Evolution

  2016cites this paper
• Retrotransposons as regulators of gene expression

  2016cites this paper
• Restricting retrotransposons: a review

  2016cites this paper
• DNA Methylation within Transcribed Regions

  2015cites this paper