Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Massively Parallel Characterization and Prediction of Disease-Associated Branch Site Variants that Perturb RNA Splicing

ABSTRACT: It is estimated that 10-30% of disease-associated genetic variants affect splicing. Splicing variants may generate deleteriously altered gene product and are potential therapeutic targets. However, experimental diagnosis for splicing variants is time-consuming and reliable computational prediction tools have not been established, especially for the 3’ end of introns. The major challenge lies in the redundant and ill-defined branch site motif therein. Here, we carried out unbiased massively parallel splicing assays on 5,307 disease-associated variants overlapped with branch sites. We observed that 11.0% (455 out of 4,154 valid comparisons) of candidate variants showed a consistent pattern of altered splicing across four experimental replicates, among which 244 candidates (6.1%) presented more than two-fold changes in the use of noncanonical splice sites and these are named high-confidence (HC) significant candidates.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179892 | GEO | 2022/05/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Branch point evolution controls species-specific alternative splicing and regulates long term potentiation

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

Branch point evolution controls species-specific alternative splicing and regulates long term potentiation

2022-12-02 | GSE208181 | GEO

Identification of New Branch Points and Unconventional Introns in Saccharomyces cerevisiae

Project description:Spliced messages constitute one-fourth of expressed mRNAs in the yeast Saccharomyces cerevisiae, and most mRNAs in metazoans. Splicing requires 5' splice site (5'SS), branch point (BP), and 3' splice site (3'SS) elements, but the role of the BP in splicing control is poorly understood because BP identification remains difficult. We developed a high-throughput method, Branch-seq, to map BP and 5'SS of isolated RNA lariats. Applied to S. cerevisiae, Branch-seq detected 76% of expressed, annotated BPs and identified a comparable number of novel BPs. We used RNA-seq to confirm associated 3'SS locations, identifying some 200 novel splice junctions, including an AT-AC intron. We show that several yeast introns use two or even three different BPs, with effects on 3'SS choice, protein coding potential, or RNA stability and identify novel introns whose splicing changes during meiosis or in response to stress. Together, these findings reveal BP-based regulation and demonstrate unanticipated complexity of splicing in yeast. 1 Lariat-seq experiment library. 3 barcoded Branch-seq libraries that make up one experiment. 26 RNA-seq samples, 2 biological replicates of each.

2016-08-01 | E-GEOD-68022 | biostudies-arrayexpress

Identification of New Branch Points and Unconventional Introns in Saccharomyces cerevisiae

2016-08-01 | GSE68022 | GEO

LaSSO, a strategy for genome-wide mapping of intronic lariats and branch-points using RNA-seq

Project description:Both canonical and alternative splicing of RNAs is governed by intronic sequence elements and produces transient lariat structures fastened by branch-points within introns. To map precisely the location of branch-points on a genomic scale, we developed LaSSO (Lariat Sequence Site Origin), a data-driven algorithm which utilizes RNA-seq data. Using fission yeast cells lacking the debranching enzyme Dbr1, LaSSO not only accurately identified canonical splicing events, but also pinpointed novel, but rare, exon-skipping events, which may reflect aberrantly spliced transcripts. Compromised intron turnover perturbed gene regulation at multiple levels, including splicing and protein translation. Notably, Dbr1 function was also critical for the expression of mitochondrial genes, and for the processing of self-spliced mitochondrial introns. LaSSO showed better sensitivity and accuracy than algorithms used for computational branch-point prediction or for empirical branch-point determination. Even when applied to a human data set acquired in the presence of debranching activity, LaSSO identified both canonical and exon skipping branch-points. LaSSO thus provides an effective, accurate and unbiased approach for defining high-resolution maps of branch-site sequences and intronic elements on a genomic scale. LaSSO should be useful to validate introns and uncover branch-point sequences in any eukaryote, and it could be integrated to RNA-seq pipelines.

2014-03-18 | GSE50246 | GEO

LaSSO, a strategy for genome-wide mapping of intronic lariats and branch-points using RNA-seq

2014-03-18 | E-GEOD-50246 | biostudies-arrayexpress

Massively Parallel Characterization and Prediction of Disease-Associated Branch Site Variants that Perturb RNA Splicing

Project description:Massively Parallel Characterization and Prediction of Disease-Associated Branch Site Variants that Perturb RNA Splicing

| PRJNA745470 | ENA

Branch retinal vein occlusion in a porcine model

Project description:Branch retinal vein occlusion (BRVO) is a common retinal vascular disease, but global protein changes following the disease remain largely unelucidated. To bring new insights into pathological processes and elucidate potential therapeutic targets, large-scale retinal protein changes following BRVO were studied by combining a porcine model of experimental BRVO with proteomic analysis by label-free liquid chromatography mass spectrometry.

2015-07-30 | PXD001800 | Pride

Two oppositely-chargedsf3b1 mutations cause defective development, impaired immune response, and aberrant selection of intronic branch sites in Drosophila

Project description:Somatic SF3b1 mutations occur in many cancers, and the highly conserved H662 residue is one of the most frequently mutated sites. To address their mechanism on splicing alteration and effects on development, we constructed mutant strains at the corresponding residue H698 in Drosophila using CRISPR-Cas9 system. Two mutations, H698D and H698R, were selected due to their presence in patients and the significantly opposite charges. Both the sf3b1-H698D and –H698R mutant flies exhibit developmental defects including less egg-laying, decreased hatching rates, delayed morphogenesis and shorter lifespan. Interestingly, the H698D mutant has decreased resistance to fungi infection, while the H698R mutant has impaired climbing ability. Further RNA-seq data finds altered expression of immunity response genes and changed alternative splicing of muscle and neural-related genes in the two mutants respectively. Lariat sequencing reveal that the sf3b1-H662 mutations cause aberrant selection of multiple intronic branch sites and the H698R mutant prefers to use upstream branch sites in the alternative splicing changed events. This study provides in vivo evidence from Drosophila to elucidate how the highly conserved SF3b1 cancer mutations alter splicing and their consequences in the development and immune systems.

2021-10-08 | GSE171002 | GEO

mRNA Transcriptase’s Analyses That Cotton fruit branch Development Status after silenced GhBRC1 gene byVIGS

Project description:Purpose: found out the regulated genes of nulliplex-branch and its forming molecular mechanism Methods: the GhBRC1 genes of nulliplex branch and short branch cotton are silenced by VIGS, and then the shoot apical mRNA of controls and treated were sequenced, in four repeats, using Illumina HiSeq 2000. Results: we found 3519 and 17 differnent expressed genes in nulliplex-branch and short branch cotton, respectively. Conclusions: Our study represents the genes control development of lateral branch.

2019-12-28 | GSE142638 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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