Transposable element exonization by non-canonical splicing generates a diversity reservoir of functional protein isoforms
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ABSTRACT:
PROVIDER: PRJNA980573 | ENA |
REPOSITORIES: ENA
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Project description:mRNA splicing enlarges the diversity of the protein repertoire, mainly through alternative exon retention or skipping. Although non-canonical splicing variants that exonize intronic regions were recently identified at the mRNA level, their contribution to the cellular proteome remains unclear. Here, we describe a population of 1300 unannotated protein isoforms generated by non-canonical splicing between exons and transposable elements (TE) using a combination of transcriptome assembly, ribosome profiling, and mass spectrometry. Despite being shorter and expressed at lower levels, their translation efficiency is similar to that of canonical isoforms, and they are shared between individuals. Functional analyses of 5 different non-canonical isoforms show stable expression, specific intracellular localization, and modified functions, as compared to the corresponding canonical isoforms. Non-canonical isoforms derive mainly from evolutionarily ancient genes and are a preferential source of alternative splicing upon which natural selection can act. We conclude that recently exonized TE isoforms are potentially functional and represent a diversity reservoir of novel protein isoforms.
2024-12-12 | GSE234223 | GEO
Project description:Background: The small RNAs that Transposable Elements generate are vastly different when they are transcriptionally silenced compared to when they are transcriptionally activated. We performed the deep sequencing of small RNAs in a number of small RNA biogenesis mutants in both Transposable Element-silenced and Transposable Element-active epigenome backgrounds. Results: We found that Transposable Elements generate large amounts of 21-22nt siRNAs only when they are transcriptionally active. These 21-22nt siRNAs are incorporated into the AGO6 protein. Conclusion: Ago6 is the key protein that bridges the post-transcriptional degradation of Transposable Element mRNAs and the establishment of DNA methylation. Examination of flower bud small RNAs from wild type and 5 single or double mutant combinations, many of which have biological replicates. In addition, IP purification of the AGO6 protein (and mock no-antigen controls) followed by sequencing of the incorporated small RNAs. Replicate A for Col and ddm1 are submitted in GSE41755
2014-11-14 | E-GEOD-57191 | biostudies-arrayexpress
Project description:Background: The small RNAs that Transposable Elements generate are vastly different when they are transcriptionally silenced compared to when they are transcriptionally activated. We performed the deep sequencing of small RNAs in a number of small RNA biogenesis mutants in both Transposable Element-silenced and Transposable Element-active epigenome backgrounds. Results: We found that Transposable Elements generate large amounts of 21-22nt siRNAs only when they are transcriptionally active. These 21-22nt siRNAs are incorporated into the AGO6 protein. Conclusion: Ago6 is the key protein that bridges the post-transcriptional degradation of Transposable Element mRNAs and the establishment of DNA methylation.
2014-11-14 | GSE57191 | GEO
Project description:Purpose: Overexpression of tau isoforms has been linked to neurodegenerative diseases, and abnormal tau expression is correlated with genomic instability. The purpose of this study is to use RNA-sequencing and molecular biological techniques to determine if there are any unique genomic consequences associated with overexpression of one or more tau isoforms. Methods: SHSY-5Y cells were infected in triplicate with lentiviruses to induce overexpression of 3R and 4R tau isoforms, were treated with amyloid-beta oligomers or DMSO, and were differentiated into neurons using retinoic acid. After RNA collection via TRIzol, poly(A)-selected, 100 bp, paired-end library preparation and sequencing were completed by the IGM Genomics Center, University of California, San Diego, La Jolla, CA, using an Illumina NovaSeq 6000 that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929). Trimmed FASTQ files were aligned to GRCH38 using STAR and differential expression of genes and transposable elements was determined using DESeq2 and software from TEToolkit (available from the Hammell Lab at Cold Spring Harbor Laboratory). Results: Our RNA-seq analysis revealed similar gene and transposable element expression patterns between cells overexpressing tau isoforms and patients with Alzheimer's disease or progressive supranuclear palsy. We found widespread differential expression particularly in L1 and Alu transposable elements and upregulation of genes related to extracellular matrix organization, focal adhesions, and cell junctions, among other biological processes. Conclusions: Our study is the first to our knowledge to examine locus-specific transposable element expression in the context of tauopathies, and to our knowledge is the first to specifically examine transposable element expression stemming from overexpression of tau isoforms. Our study provides additional evidence that transposable elements may play a role in tauopathies and provides further insight into the locations of transposable element expression in the genome in the context of neurodegenerative diseases.
2021-09-12 | GSE163150 | GEO
Project description:Background: Transposable element 24 nucleotide small RNAs are not efficiently incorporated into the AGO1 protein, which is involved in endogenous RNAi and gene regulation through the microRNA and tasiRNA pathways. Results: The AGO1 protein incorporates large quantities of transposable element siRNAs when transposable elements are epigenetically activated and transcribed. The incorporation of transposable element siRNAs is at the expense of the most abundant microRNAs. These transposable element siRNAs can act as tasiRNAs, regulating genes that they have partial complementarity to. Conclusion: Transposable element small RNAs are more dynamic than previously thought. They can be incorporated into AGO1 and regulate genes. Three biological replicates of small RNA sequencing from two genotypes
2014-04-07 | E-GEOD-45990 | biostudies-arrayexpress
Project description:Epigenomic conservation of transposable element silencing
| PRJNA379439 | ENA
Project description:Background: Transposable element 24 nucleotide small RNAs are not efficiently incorporated into the AGO1 protein, which is involved in endogenous RNAi and gene regulation through the microRNA and tasiRNA pathways. Results: The AGO1 protein incorporates large quantities of transposable element siRNAs when transposable elements are epigenetically activated and transcribed. The incorporation of transposable element siRNAs is at the expense of the most abundant microRNAs. These transposable element siRNAs can act as tasiRNAs, regulating genes that they have partial complementarity to. Conclusion: Transposable element small RNAs are more dynamic than previously thought. They can be incorporated into AGO1 and regulate genes.
2014-04-07 | GSE45990 | GEO
Project description:Background: Transposable elements are known to influence the regulation of some genes. We aimed to determine which genes show altered gene expression when transposable elements are epigenetically activated. Results: We find over 2000 genes with altered steady-state expression levels in ddm1 mutants. Some of these genes are influenced by neighboring transposable element fragments, while other genes are targeted by transposable element derived 21 nucleotide siRNAs. Conclusion: The regulation of the genic portion of the Arabidopsis genome is heavily influenced by the epigenetic regulation of transposable elements. The regulation of genes by transposable elements can occur through multiple mechanisms. Three biological replicates for two genotypes
2014-04-07 | E-GEOD-46050 | biostudies-arrayexpress
Project description:Investigation of the effect of the knockdown of AT-hook motif DNA binding nuclear matrix protein TRANSPOSABLE ELEMENT KILLER (TEK) in the Arabidopsis Landsberg erecta (Ler) background Transposable elements (TEs) are silenced by epigenetic mechanisms of DNA and histone methylation. The repressive histone modification H3 lysine 9 dimethylation (H3K9me2) is TE-associated epigenetic hallmark, and is necessary for DNA methylation. However the mechanism to direct the repressive epigenetic modification in TEs has remained elusive. Here we show that knockdown of the AT-hook motif DNA binding nuclear matrix protein TRANSPOSABLE ELEMENT KILLER (TEK) in the Arabidopsis Landsberg erecta (Ler) background results in robust activation of various TEs, the repeat-containing floral repressor gene FWA and the TE-containing floral repressor FLOWERING LOCUS C (FLC). A four chip study using two separate wild-type seedling mRNA samples and two separate TEKi seedling mRNA samples
2012-09-12 | E-GEOD-39158 | biostudies-arrayexpress
Project description:Transposable elements, known colloquially as “jumping genes,” constitute approximately 45% of the human genome. Cells utilize epigenetic defenses to limit transposable element jumping, including formation of silencing heterochromatin and generation of piwi-interacting RNAs (piRNAs), small RNAs that facilitate clearance of transposable element transcripts. Here we identify transposable element activation as a key mediator of neuronal death in tauopathies, a group of neurodegenerative disorders, including Alzheimer’s disease, that are pathologically characterized by deposits of tau protein in the brain. Mechanistically, we find that heterochromatin decondensation and reduction of piwi/piRNAs drive transposable element activation in tauopathy. Using genetic and pharmacological approaches in a Drosophila melanogaster model of tauopathy, we provide evidence for a causal relationship between pathogenic tau-induced heterochromatin decondensation, piwi/piRNA depletion, active transposable element obilization, and neurodegeneration. We further report a significant increase in transcripts of the endogenous retrovirus class of transposable elements in human Alzheimer’s disease and progressive supranuclear palsy, suggesting that transposable element dysregulation is conserved in human tauopathy. Taken together, our data identify heterochromatin decondensation, piwi/piRNA depletion and consequent transposable element activation as a novel, pharmacologically targetable, mechanistic driver of neurodegeneration in tauopathy.
2018-07-04 | GSE115606 | GEO