Species-specific splicing differences are primarily governed by changes in cis-acting sequences
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Qun Pan
PROVIDER: E-GEOD-31454 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We assessed whether human transcripts expressed in an aneuploid mouse that carries human chromosome 21 (HsChr21) are spliced in a human-specific or mouse-specific fashion. In almost all cases, human-specific alternative splicing is maintained in the mouse nucleus. Species-specific splicing therefore appears to be primarily directed by cis-acting elements, rather than changes in the levels or activities of trans-acting factors.
2012-12-01 | GSE31454 | GEO
Project description:Species-specific splicing differences are primarily governed by changes in cis-acting sequences
| PRJNA145829 | ENA
Project description:Abstract: Alternative splicing (AS) plays a major role in the generation of proteomic diversity and in gene regulation. However, the role of the basal splicing machinery in regulating AS remains poorly understood. Here we show that the core snRNP protein SmB/B’ self-regulates its expression by promoting the inclusion of a highly-conserved alternative exon in its own pre-mRNA that targets the spliced transcript for nonsense-mediated mRNA decay (NMD). Depletion of SmB/B’ in human cells results in reduced levels of snRNPs and in a striking reduction in the inclusion levels of hundreds of alternative exons, with comparatively few effects on constitutive exon splicing levels. The affected alternative exons are enriched in genes encoding RNA processing and other RNA binding factors, and a subset of these exons also regulate gene expression by activating NMD. Our results thus demonstrate a role for the core spliceosomal machinery in controlling an exon network that appears to modulate the levels of many RNA processing factors. HeLa cells were transfected with a control non-targeting siRNA pool (siNT), or with siRNA pools designed to knockdown SmB/B' or SRSF1 (also known as SF2/ASF/SFRS1). Sequence reads were aligned to exon-exon junction sequences in a database of EST/cDNA-mined cassette-type alternative splicing events. Processed data files (.bed and .txt) provided as supplementary files on the Series record. Processed data file build information: hg18.
2011-02-01 | E-GEOD-26463 | biostudies-arrayexpress
Project description:By combining deep sequencing with high-throughput quantitative RT-PCR, we reveal that somatic splicing profiles are reorganized to pluripotent splicing profiles during reprogramming from mouse embryonic fibroblasts (MEFs) to induced pluripotent stem (iPS) cells. The splicing pattern in pluripotent stem cells resembles that in testis, and the regulatory regions have specific characters in length and sequence. These results indicate that the dynamic alteration in splicing is an integral part of the molecular network involved in the reprogramming process. Sequencing data from MEF, two iPS cell lines and one ES cell line. RT-PCR data will be represented within Figures or Tables in published manuscripts.
2013-10-17 | E-GEOD-46149 | biostudies-arrayexpress
Project description:Recent analyses of 5-hydroxymethylcytosine (5hmC) suggest that the modified base influences transcription by acting as an intermediate to demethylation. However, elevated levels of 5hmC within neural tissues suggest that the mark is stable and may directly contribute to gene regulation. Here, we characterize the in vivo genomic patterning and stability of 5hmC in three defined developmental states of the mouse main olfactory epithelium – multipotent stem cells, neuronal progenitors, and mature olfactory sensory neurons. 5hmC is globally enriched in neuronal progenitors and neurons relative to the stem population with significant enrichment on the bodies of transcriptionally active genes and intergenic enhancers. Although gene body 5hmC levels are positively correlated with cell type-specific gene expression in all developmental stages, genes that are commonly expressed within both neuronal progenitors and mature neurons experience the greatest increases in 5hmC levels. Moreover, enriched levels of the modified base on intergenic conserved regions correlate with cell type-specific expression of nearby genes and coincide with developmentally regulated enhancer-promoter interaction at one locus examined. Finally, an analysis of two-month old neurons indicates that elevated 5hmC levels persist in fully differentiated neurons. Together, these data suggest that 5hmC stabilizes the expression of developmentally active genes through effects at both gene bodies and intergenic regulatory elements. 9 Samples
2013-09-03 | E-GEOD-38604 | biostudies-arrayexpress
Project description:Influenza B viruses evolve more slowly than human influenza A, but no reasons for the difference have been established. We have analyzed sequence changes in the hemagglutinin and neuraminidase of influenza B viruses (and have determined four hemagglutinin sequences, of B/Bonn/43, B/USSR/100/83, B/Victoria/3/85, and B/Memphis/6/86) in relation to antigenic properties and compared these with similar analyses of variation in influenza A antigens. Independent of the slower rate of change in influenza B antigens, only approximately 30% of nucleotide changes in either the hemagglutinin or neuraminidase gene sequence result in amino acid changes in the protein, whereas in influenza A 50% of nucleotide changes result in altered amino acids. Thus, there is less selection for change, or less tolerance to change, in the influenza B antigens. This is similar to findings with influenza C and findings with influenza A viruses that replicate in lower animals and birds and is closer to the type of variation found in other RNA viruses. We propose that human influenza A is unique in that it is the only virus group in which antibody selection dominates evolutionary change.
| S-EPMC54008 | biostudies-other
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:We carried out the first analysis of alternative splicing complexity in human tissues using mRNA-Seq data. New splice junctions were detected in 20% of multiexon genes, many of which are tissue specific. By combining mRNA-Seq and EST-cDNA sequence data, we estimate that transcripts from 95% of multiexon genes undergo alternative splicing and that there are 100,000 intermediate- to high-abundance alternative splicing events in major human tissues. From a comparison with quantitative alternative splicing microarray profiling data, we also show that mRNA-Seq data provide reliable measurements for exon inclusion levels. Keywords: mRNA expression 32-nucleotide sequence reads from six human tissues including brain, cerebral cortex, heart, liver, lung and skeletal muscle.
2008-11-19 | E-GEOD-13652 | biostudies-arrayexpress
Project description:A proportion of the genetic variants underlying complex phenotypes do so through their effects on gene expression, so an important challenge in complex trait analysis is to discover the genetic basis for the variation in transcript abundance. So far, the potential of mapping both quantitative trait loci (QTLs) and expression quantitative trait loci (eQTLs) in rodents has been limited by the low mapping resolution inherent in crosses between inbred strains. We provide a megabase resolution map of thousands of eQTLs in hippocampus, lung, and liver samples from heterogeneous stock (HS) mice in which 843 QTLs have also been mapped at megabase resolution. We exploit dense mouse SNP data to show that artifacts due to allele-specific hybridization occur in _30% of the cis-acting eQTLs and, by comparison with exon expression data, we show that alternative splicing of the 3_ end of the genes accounts for <1% of cis-acting eQTLs. Approximately one third of cis-acting eQTLs and one half of trans-acting eQTLs are tissue specific. We have created an important systems biology resource for the genetic analysis of complex traits in a key model organism.
2009-10-22 | E-MTAB-88 | biostudies-arrayexpress
Project description:<p>RNA sequencing was performed on human DRGs and relative gene abundances were calculated.</p> <p>Various analyses were performed:</p> <p> <ol> <li>Human DRG gene expression profiles were contrasted with a panel of gene expression profiles of relevant tissues in human and mouse ( integrating, among other sources, datasets from ENCODE and GTex ) in order to identify.</li> <ol type="a"> <li>DRG-enriched gene expression, co-expression modules of DRG-expressed genes, and key transcriptional regulators in humans.</li> <li>Contrasting the human and mouse DRG transcriptomes to identify DRG-enriched gene expression patterns that were conserved between human and mouse, identifying putative cell types of expression of these genes, and potential known drugs that might target the corresponding gene products.</li> <li>Characterization of non-coding RNA profile of human and mouse DRGs.</li> <li>Characterization of DRG-enriched alternative splicing and alternative transcription start site usage based transcript variants in humans and mouse, and the overlap between these two species.</li> <li>Contrasting of human DRG and GTex human tibial nerve samples to identify putative axonally transported mRNAs in sensory neurons.</li> </ol> <li>Human DRG transcriptomes from donors suffering from neuropathic and/or chronic pain were contrasted with controls to identify.</li> <ol type="a"> <li>Differentially expressed genes, pathways and regulators path play a potential role in neuronal plasticity, electrophysiological activity, immune signaling and response.</li> <li>Predictive models (Random Forests) were built to jointly predict the sex and pain state of samples based on information contained solely in autosomal gene expression profile.</li> <li>Gene co-expression modules were identified and gene set enrichment analysis performed.to identify sample - pathway associations, and to broadly characterize plasticity in human DRG cell types.</li> </ol> </ol> </p>
| phs001158 | dbGaP