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SRP110976
Mus musculus
30 Downloadable Samples
Illumina Genome Analyzer II
Description
The roles of RNA-binding proteins as chaperones in the lifecycles of mRNAs are not well understood. The mammalian mitochondrial genome has been compressed over evolution to a size of just 16 kb, nevertheless the expression of its genes requires transcription, RNA processing, translation and RNA decay, much like the more complex chromosomal systems, providing an opportunity to use it as a model system to understand the fundamental aspects of gene expression. Here we combine RNase footprinting with PAR-CLIP at unprecedented depth to reveal the importance of RNA-protein interactions guided by the LRPPRC/SLIRP complex in dictating RNA folding within the mitochondrial transcriptome. We show that LRPPRC, in complex with its protein partner SLIRP, binds throughout the mitochondrial transcriptome, with a preference for mRNAs, and its loss affects the entire secondary structure and stability of the transcriptome. We demonstrate that the LRPPRC/SLIRP complex is a global RNA chaperone that stabilizes RNA structures to expose the required sites for translation, stabilization and polyadenylation. Our findings reveal a general mechanism where extensive RNA-protein interactions ensure that RNA is accessible for its biological functions. Overall design: RNase footprinting of LRPPRC and SLIRP knockout and control mice, in technical duplicate.
Publication Title
LRPPRC-mediated folding of the mitochondrial transcriptome.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic and epigenetic determinants of neurogenesis and myogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The regulatory networks of differentiation programs have been partly characterized; however, the molecular mechanisms of lineage-specific gene regulation by highly similar transcription factors remain largely unknown. Here we compare the genome-wide binding and transcription profiles of NEUROD2-mediated neurogenesis with MYOD-mediated myogenesis. We demonstrate that NEUROD2 and MYOD bind a shared CAGCTG E-box motif and E-box motifs specific for each factor: CAGGTG for MYOD and CAGATG for NEUROD2. Binding at factor-specific motifs is associated with gene transcription, whereas binding at shared sites is associated with regional epigenetic modifications but not as strongly associated with gene transcription. Binding is largely constrained to E-boxes pre-set in an accessible chromatin context that determines the set of target genes activated in each cell type. These findings demonstrate that the differentiation program is genetically determined by E-box sequence whereas cell lineage epigenetically determines the availability of E-boxes for each differentiation program.
Publication Title
Genetic and epigenetic determinants of neurogenesis and myogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Investigate the genome-wide gene expression profiles of 50% and 95% confluent C2C12 myoblasts and C2C12 myotubes differentiated for 24 and 48 hours.
Publication Title
Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Facioscapulohumeral dystrophy (FSHD) is one of the most common inherited muscular dystrophies. The causative gene remains controversial and the mechanism of pathophysiology unknown. Here we identify genes associated with germline and early stem cell development as targets of the DUX4 transcription factor, a leading candidate gene for FSHD. The genes regulated by DUX4 are reliably detected in FSHD muscle but not in controls, providing direct support for the model that misexpression of DUX4 is a causal factor for FSHD. Additionally, we show that DUX4 binds and activates LTR elements from a class of MaLR endogenous primate retrotransposons and suppresses the innate immune response to viral infection, at least in part through the activation of DEFB103, a human defensin that can inhibit muscle differentiation. These findings suggest specific mechanisms of FSHD pathology and identify candidate biomarkers for disease diagnosis and progression.
Publication Title
DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 112 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 45 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Data from tc-, nt- and p-RNA as well as 1 and 2h of actinomycin-D treatment (5g/ml) of NIH-3T3 cells used to determine half-lives. RNA was labeled for 15, 30 or 60 minutes with 4-thiouridine. After preparation of tc-RNA, thiol-labeled RNA was biotinylated using biot-HPDP and subsequently tc-RNA was separated into nt- and p-RNA using streptavidin coated magnetic beads. All three fractions were used for microarray analysis. For actinomycin-D experiments only tc-RNA was used prepared from cell before and 1 an 2h after addition of act-D.
Publication Title
Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
RNA was labeled in BL41 cells by culturing cells for 60 min in media containing 100M 4sU. Tc-RNA was separated into nt- and p-RNA. All three RNA subsets were subjected to microarray analysis. Only probe sets providing present calls in all RNA samples/subsets were included into the analysis
Publication Title
Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Expression data from NIH-3T3 cells treated with mock, 100 U/ml IFN alpha or 100 U/ml gamma for 1 or 3h on nt-RNA labeled for 30-60 min at different times of interferon treatment
Publication Title
High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Differential gene expression caused by 1h and 3h of IFN alpha or gamma treatment was analyzed in total cellular RNA of NIH-3T3 cells compared to mock
Publication Title
High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay.
Sample Metadata Fields
No sample metadata fields
View Samples