Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transposable element exonization by non-canonical splicing generates a diversity reservoir of functional protein isoforms

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234223 | GEO | 2024/12/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The dynamic landscape of fission yeast meiosis alternative-splice isoforms

Project description:Alternative splicing increases the diversity of transcriptomes and proteomes in metazoans. The extent to which alternative splicing is active and functional in unicellular organisms is less understood. Here we exploit a single-molecule long-read sequencing technique and develop a computational tool, SpliceHunter, to characterize the transcriptome in the meiosis of fission yeast. We reveal 17017 alternative splicing events in 19741 novel isoforms at different stages of meiosis, including antisense and read-through transcripts. Intron retention is the major type of alternative splicing, followed by “alternate intron in exon”. 887 novel transcription units are detected; 60 of the predicted proteins show homology in other species and form theoretical stable structures. We compare the dynamics of novel isoforms based on the number of supporting full-length reads with those of annotated isoforms and explore the translational capacity and quality of novel isoforms. The evaluation of these factors indicates that the majority of novel isoforms are unlikely to be both condition-specific and translatable but the possibility of functional novel isoforms is not excluded. Together, this study highlights the diversity and dynamics at the isoform level in the sexual development of fission yeast.

2016-11-10 | GSE79802 | GEO

Widespread Use of Non-Productive Alternative Splice Sites in Saccharomyces cerevisiae

Project description:Using RNA-Seq analysis of nonsense-mediated mRNA decay (NMD) mutant strains, we show that many Saccharomyces cerevisiae intron-containing genes exhibit usage of alternative splice sites, but most transcripts generated by splicing from these sites are non-functional because they introduce premature termination codons leading to transcript degradation by NMD. Analysis of splicing mutants combined with NMD inactivation revealed the role of specific splicing factors in governing the use of these alternative splice sites and identified novel functions for Prp17p in enhancing the use of branchpoint-proximal upstream 3M-bM-^@M-^Y splice sites and for Prp18p in suppressing the usage of a non-canonical AUG 3M-bM-^@M-^Y-splice site. The use of non-productive alternative splice sites can limit the expression of some transcripts and can be increased in stress conditions in a promoter-dependent manner, contributing to the down-regulation of genes during stress. These results reveal that alternative splicing is frequent in S.cerevisiae but masked by RNA degradation and that the use of alternative splice sites is mostly aimed at controlling transcript levels rather than increasing proteome diversity. mRNA-Seq profiling of 3 mutants in the nonsense-mediated mRNA decay pathway and wildtype yeast

2014-02-21 | E-GEOD-55213 | biostudies-arrayexpress

Full-length autonomous transposable elements are preferentially targeted by expression-dependent forms of RNA-directed DNA methylation

Project description:The diversity of small RNA-directed DNA methylation (RdDM) mechanisms have been underestimated due to the nearly complete transcriptional silencing of transposable elements (TEs) in the wild-type reference strains of Arabidopsis thaliana. In plants mutant for the SWI/SNF histone remodeler DDM1, TEs are globally activated due to loss of genome wide heterochromatin condensation. Transcriptionally activated TEs go through additional non-canonical forms of RdDM that are dependent on RNA Polymerase II expression. However, the global targets of the non-canonical RdDM pathway have not been explored. In an attempt to identify and contrast the targets of canonical and expression-dependent non-canonical RdDM, we performed MethylC-seq of genome-wide DNA methylation patterns from several RdDM mutants in either the TE-silent or the TE-active (ddm1) contexts. Arabidopsis wildtype and twenty RdDM pathway mutants

2016-07-22 | E-GEOD-79746 | biostudies-arrayexpress

Transposable element exonization by non-canonical splicing generates a diversity reservoir of functional protein isoforms

Project description:Transposable element exonization by non-canonical splicing generates a diversity reservoir of functional protein isoforms

| PRJNA980573 | ENA

Comparing the targets of distinct RNA Directed DNA Methylation mechanisms in Arabidopsis thaliana

Project description:The diversity of small RNA-directed DNA methylation (RdDM) mechanisms have been underestimated due to the nearly complete transcriptional silencing of transposable elements (TEs) in the wt Col ecotype of Arabidopsis thaliana. In plants mutant for the SWI/SNF2 histone remodeler DDM1, TEs are globally activated due to loss of genome wide heterochromatin condensation. Activated TEs go through additional non-canonical forms of RdDM. However, the global targets of the non-canonical RdDM pathway are unidentified. In an attempt to identify and contrast the targets of canonical and non-canonical RdDM, we sequenced small RNAs from several RdDM mutants in either the TE-silent or the TE-active (ddm1) contexts. Examination of unopened flower bud small RNAs from wild type and various single or double mutant combinations, many of which have biological replicates. Small RNA sequences from wt Col, controls and other mutants shown in the study are available at GSE41755 and GSE57191.

2016-07-22 | E-GEOD-79780 | biostudies-arrayexpress

Comparing the targets of distinct RNA Directed DNA Methylation mechanisms in Arabidopsis thaliana

Project description:The diversity of small RNA-directed DNA methylation (RdDM) mechanisms have been underestimated due to the nearly complete transcriptional silencing of transposable elements (TEs) in the wt Col ecotype of Arabidopsis thaliana. In plants mutant for the SWI/SNF2 histone remodeler DDM1, TEs are globally activated due to loss of genome wide heterochromatin condensation. Activated TEs go through additional non-canonical forms of RdDM. However, the global targets of the non-canonical RdDM pathway are unidentified. In an attempt to identify and contrast the targets of canonical and non-canonical RdDM, we sequenced small RNAs from several RdDM mutants in either the TE-silent or the TE-active (ddm1) contexts.

2016-07-22 | GSE79780 | GEO

Tollip isoforms as key regulators of macrophage phenotype and response to LPS

Project description:Pathogen recognition via the Toll-like receptor (TLR) signaling pathways leads to inflammatory responses by innate immune cells. The Toll-interacting protein (Tollip) is an ubiquitin-binding protein which negatively regulates TLR signaling. We have previously described extensive alternative splicing of Tollip in human and mouse macrophages. In the current study we examined the role of two mouse Tollip isoforms in innate immune responses: the canonical full-length form (Tollip.a), and a novel 220 amino acid isoform (Tollip.b), which lacks the Ub-binding domain. We hypothesized that alternative splicing of this negative regulator contributes to the diversification of macrophage responses to pathogens. The function of the two Tollip isoforms was studied by over-expressing the variants in the macrophage-like cell line, RAW264.7.

2010-09-18 | E-TABM-795 | biostudies-arrayexpress

Non-canonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent neo-antigens in cancer patients

Project description:ost characterized tumor antigens are ‘genomic’, i.e. encoded by canonical, non-canonical or somatically mutated genomic sequences. We investigate here the presentation and immunogenicity of tumor antigens derived from non-canonical mRNA splicing events between coding exons and transposable elements (TEs). Comparing non-small cell lung cancer (NSCLC), an immunogenic tumor type, and diverse non-tumor tissues, we identify several thousand splicing junctions between exons and diverse TE classes. A subset of these junctions is both tumor-specific and shared across patients. HLA-I peptidomic identifies peptides encoded by tumor-specific junctions in primary NSCLC samples and lung tumor cell lines. Recurrent junction-encoded peptides are immunogenic in vitro and CD8+ T cells specific for junction-encoded epitopes are present in tumors and tumor-draining lymph nodes from NSCLC patients. We conclude that non-canonical splicing junctions between exons and TEs represent a source of recurrent, immunogenic tumor-specific antigens in NSCLC cancer patients.

2023-02-27 | PXD034820 | Pride

Widespread Use of Non-Productive Alternative Splice Sites in Saccharomyces cerevisiae

Project description:Using RNA-Seq analysis of nonsense-mediated mRNA decay (NMD) mutant strains, we show that many Saccharomyces cerevisiae intron-containing genes exhibit usage of alternative splice sites, but most transcripts generated by splicing from these sites are non-functional because they introduce premature termination codons leading to transcript degradation by NMD. Analysis of splicing mutants combined with NMD inactivation revealed the role of specific splicing factors in governing the use of these alternative splice sites and identified novel functions for Prp17p in enhancing the use of branchpoint-proximal upstream 3’ splice sites and for Prp18p in suppressing the usage of a non-canonical AUG 3’-splice site. The use of non-productive alternative splice sites can limit the expression of some transcripts and can be increased in stress conditions in a promoter-dependent manner, contributing to the down-regulation of genes during stress. These results reveal that alternative splicing is frequent in S.cerevisiae but masked by RNA degradation and that the use of alternative splice sites is mostly aimed at controlling transcript levels rather than increasing proteome diversity.

2014-02-21 | GSE55213 | GEO

Widespread regulated alternative splicing of single codons accelerates proteome evolution

Project description:Thousands of human genes contain introns ending in NAGNAG motifs (N any nucleotide), where both NAGs can function as 3' splice sites, yielding isoforms differing by inclusion/exclusion of just three bases. However, the functional importance of NAGNAG alternative splicing is highly controversial. Using very deep RNA-Seq data from sixteen human and eight mouse tissues, we found that approximately half of alternatively spliced NAGNAGs undergo tissue-specific regulation and that regulated events have been selectively retained: alternative splicing of strongly tissue-specific NAGNAGs was ten times as likely to be conserved between species as for non-tissue-specific events. Further, alternative splicing of human NAGNAGs was associated with an order of magnitude increase in the frequency of exon length changes at orthologous mouse/rat exon boundaries, suggesting that NAGNAGs accelerate exon evolution. Together, our analyses show that NAGNAG alternative splicing constitutes a major generator of tissue-specific proteome diversity and accelerates evolution of proteins at exon-exon boundaries. mRNA-Seq of sixteen human and eight mouse tissues. Supplementary files: human.nagnag.junctions.gff and mouse.nagnag.junctions.gff are the annotation files (in GFF3 format) corresponding to the 'bwtout' mapped reads files linked to the Sample records. Raw data files provided for Samples GSM742937-GSM742952 only.

2012-01-05 | E-GEOD-30017 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data