Genome-wide analysis of alternative splicing evolution among Mus subspecies
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus musculus Mus musculus domesticus Mus spretus Mus musculus castaneus
PROVIDER: GSE18905 | GEO | 2010/02/28
SECONDARY ACCESSION(S): PRJNA121315
REPOSITORIES: GEO
Similar Datasets
Project description:We studied the evolution of alternative splicing in the early stages of species divergence in the house mouse. We sequenced the testis transcriptomes of three Mus musculus subspecies and Mus spretus using Illumina technology. On the basis of a genome-wide analysis of read coverage differences among subspecies, we identified several hundred candidate alternatively spliced regions.
2010-02-28 | E-GEOD-18905 | biostudies-arrayexpress
Project description:Genome-wide analysis of alternative splicing evolution among Mus subspecies
| PRJNA121315 | ENA
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
Project description:Regulation and functionality of species-specific alternative splicing has remained enigmatic for many years. Calcium/calmodulin-dependent protein kinase IIβ (CaMKIIβ) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific CAMK2B splice isoforms, which show altered kinetic properties and changes in substrate specificity. Furthermore, we demonstrate that primate-specific Camk2β alternative splicing is achieved through branch point weakening during evolution. We show that reducing branch point and splice site strength during evolution globally renders constitutive exons alternative, thus providing a paradigm for cis-directed species-specific alternative splicing regulation. Using CRISPR/Cas9 we introduced the weaker human branch point into the mouse genome, resulting in human-like CAMK2B splicing in the brain of mutant mice. We observe a strong impairment of long-term potentiation in CA3-CA1 synapses of mutant mice, thus connecting branch point-controlled, species-specific alternative splicing with a fundamental function in learning and memory.
2022-12-19 | PXD035346 | Pride
Project description:To uncover the possible regulatory mechanism in regulatory alternative splicing in plants evolution, we used RNA-seq to compare the transcriptomes in Arabidopsis ecotypes Col and C24. We found different class of AS types have different regulatory mechanisms in Arabidopsis and divergence of alternative splicing in different class is varied in evolution. Sequence variation analysis had found evolution divergent AS events significantly altered their sequences compared to conserved events and the variation is AS class specific.
2018-04-23 | GSE62478 | GEO
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.
2012-01-05 | GSE30017 | GEO
Project description:Regulation and functionality of species-specific alternative splicing has remained enigmatic for many years. Calcium/calmodulin-dependent protein kinase IIβ (CaMKIIβ) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific CAMK2B splice isoforms, which show altered kinetic properties and changes in substrate specificity. Furthermore, we demonstrate that primate-specific Camk2β alternative splicing is achieved through branch point weakening during evolution. We show that reducing branch point and splice site strength during evolution globally renders constitutive exons alternative, thus providing a paradigm for cis-directed species-specific alternative splicing regulation. Using CRISPR/Cas9 we introduced the weaker human branch point into the mouse genome, resulting in human-like CAMK2B splicing in the brain of mutant mice. We observe a strong impairment of long-term potentiation in CA3-CA1 synapses of mutant mice, thus connecting branch point-controlled, species-specific alternative splicing with a fundamental function in learning and memory.
2022-12-02 | GSE208181 | GEO
Project description:The evolution of alternative splicing in glioblastoma under therapy.
| PRJNA649916 | ENA
Project description:Alternative splicing is a rich source of tumor-specific neoantigen targets for immunotherapy. This holds promise for glioblastomas (GBMs), the most common primary tumors of the adult brain, which are resistant to standard-of-care therapy. Although most clinical trials enroll patients at recurrence, most preclinical studies have been done with specimens from primary disease. There are limited expression data from GBMs at recurrence and surprisingly little is known about the evolution of splicing patterns under therapy. We profiled 29 primary-recurrent paired human GBM specimens via RNA sequencing. We describe the landscape of alternative splicing in GBM at recurrence and contrast that to primary and non-malignant brain-tissue specimens. By screening single-cell atlases, we identify cell-type specific splicing patterns and novel splicing events in cell-surface proteins that are suitable targets for engineered T-cell therapies. We identify recurrent-specific isoforms of mitogen-activated kinase pathway genes that enhance invasiveness and are preferentially expressed by stem-like cells. These studies shed light on gene expression in recurrent GBM and identify novel targets for therapeutic development.
2020-12-10 | GSE155434 | GEO
Project description:The human transcriptome is so large, diverse and dynamic that, even after a decade of investigation by RNA sequencing (RNA-Seq), we are yet to resolve its true dimensions. RNA-Seq suffers from an expression-dependent bias that impedes discovery of low-abundance transcripts and has prevented a complete census of gene expression. Here we performed targeted single-molecule and short-read RNA-Seq to survey the transcriptional landscape of a single human chromosome (Hsa21) at unprecedented resolution. Our analysis reaches the lower limits of the transcriptome and identifies a fundamental distinction between the architecture of protein-coding and noncoding gene content. Unlike their coding counterparts, noncoding exons undergo universal alternative splicing to produce a seemingly limitless variety of isoforms. Targeted RNA-Seq analysis of syntenic regions of the mouse genome shows that few noncoding exons are shared between human and mouse. Despite this divergence, human alternative splicing profiles are recapitulated on Hsa21 in mouse cells, indicative of regulation by a local splicing code that is more strongly conserved than the noncoding isoforms themselves. We propose that noncoding exons are functionally modular, with combinatorial alternative splicing generating an enormous repertoire of potential regulatory RNAs and a rich transcriptional reservoir for gene evolution.
2018-01-01 | GSE99637 | GEO