Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Yanlong Ji

LAB HEAD: Henning Urlaub

PROVIDER: PXD035346 | Pride | 2022-12-19

REPOSITORIES: pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	2021-10-27_QE_BK286_AF_AnalogSensitiveKinaseAssay_SDB_01.raw	Raw
	2021-10-27_QE_BK286_AF_AnalogSensitiveKinaseAssay_SDB_02.raw	Raw
	2021-10-27_QE_BK286_AF_AnalogSensitiveKinaseAssay_SDB_03.raw	Raw
	2021-10-27_QE_BK286_AF_AnalogSensitiveKinaseAssay_SDB_04.raw	Raw
	2021-10-27_QE_BK286_AF_AnalogSensitiveKinaseAssay_SDB_05.raw	Raw

Items per page:

1 - 5 of 37

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.

2022-12-02 | GSE208181 | GEO

Evolutionary dynamics of gene and isoform regulation in mammalian tissues

Project description:Most mammalian genes produce multiple distinct mRNAs through alternative splicing, but the extent of splicing conservation is not clear. To assess tissue-specific transcriptome variation across mammals, we sequenced cDNA from 9 tissues from 4 mammals and one bird in biological triplicate, at unprecedented depth. We find that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific. Thousands of novel, lineage-specific and conserved alternative exons were identified; widely conserved alternative exons had signatures of binding by MBNL, PTB, RBFOX, STAR and TIA family splicing factors, implicating them as ancestral mammalian splicing regulators. Our data also indicates that alternative splicing is often used to alter protein phosphorylatability, delimiting the scope of kinase signaling. Tissue transcriptomes from 9 tissues from 5 species, 3 individuals per species, were sequenced and compared (two samples for mouse_heart). <br> Curation note: E-GEOD-41637 (9 tissues, 5 organisms) has been split into five artefactual ArrayExpress experiments, one experiment per species for inclusion in Expression Atlas. Each artefactual experiment omits the processed data files (which are still available via the original E-GEOD-41637 records). Chicken: E-MTAB-2797; Cow: E-MTAB-2798; Rhesus monkey: E-MTAB-2799; Rat: E-MTAB-2800; Mouse: E-MTAB-2801

2012-12-21 | E-GEOD-41637 | biostudies-arrayexpress

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

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

| PRJNA858674 | ENA

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

FUBP1 is a core splicing factor that facilitates 3' splice site recognition and splicing of long introns [In vitro iCLIP]

Project description:Splicing is a central process in metazoans and greatly expands their proteome by alternative splicing of pre-mRNA transcripts. An essential regulatory step during early spliceosome assembly is the recognition of cis-regulatory RNA motifs in pre-mRNAs. Here, we identified the RNA binding protein FUBP1 as a novel core splicing factor with a ubiquitous footprint on pre-mRNAs. FUBP1 binds to a previously unknown cis-regulatory motif upstream of the branch point of human introns. We show that FUBP1 binds and stabilises known 3' splice site components such as the essential splicing factor U2AF2. FUBP1 mutant cell lines and patient data indicate that FUBP1 is particularly relevant for efficient splicing of exons flanked by long introns. In addition to its role at the 3’ splice site, FUBP1 shows multiple interactions with U1 snRNP- associated proteins. This demonstrates an important role for FUBP1 in splice site bridging in the context of long introns.

2023-07-27 | GSE220183 | GEO

FUBP1 is a core splicing factor that facilitates 3' splice site recognition and splicing of long introns [RNA-Seq]

2023-07-27 | GSE220180 | GEO

FUBP1 is a core splicing factor that facilitates 3' splice site recognition and splicing of long introns [In vivo iCLIP]

2023-07-27 | GSE220184 | GEO

mRNA profiling of wildtype, germline depleted, NMD mutant C. elegans whole worms and wildtype dissected gonads

Project description:Adjacent alternative 3’ splice sites, those separated by ≤18nt, provide a unique problem in the study of alternative splicing regulation; there is overlap of the cis-elements that define the adjacent sites. Identification of the intron's 3' end depends upon sequence elements that define the branchpoint, polypyrimidine tract and terminal AG dinucleotide. Starting with RNA-seq data from germline-enriched and somatic cell-enriched C. elegans samples, we identify hundreds of introns with adjacent alternative 3’ splice sites. We identify 203 events that undergo tissue-specific alternative splicing. For these, the regulation is mono-directional, with somatic cells preferring to splice at the distal 3' splice site and germline cells showing a distinct shift towards usage of the adjacent proximal 3' splice site. Splicing patterns in somatic cells follow consensus rules of 3’ splice site definition, using sites with a short stretch of pyrimidines and an AG dinucleotide. Splicing in germline cells occurs at proximal 3' splice sites that frequently lack a polypyrimidine tract or, occasionally, the AG dinucleotide. We provide evidence that use of germline-specific proximal 3' splice sites is conserved across Caenorhabditis species. We propose that divergent mechanisms exist between germline and somatic cells in determining an intron terminus at adjacent alternative 3’ splice sites. Examination of alternative splicing changes between germline- and somatic-cell enriched samples as well as nonsense-mediated decay mutants.

2015-04-22 | E-GEOD-64672 | biostudies-arrayexpress

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. Interrogation of the S. pombe transcriptome using rRNA depleted strand specific RNA sequencing (Illumina HiSeq 2000) in wild type and dbr1.M-NM-^T cultures. A total of 4 samples were analyzed: two biological repeates of wild-type strain and two biological repeats of dbr1.M-NM-^T

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