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SRP095405
Homo sapiens
52 Downloadable Samples
Illumina HiSeq 2500
Description
NOTCH1 is mutationally activated in ~15% of cases of chronic lymphocytic leukaemia (CLL), but its role in B-cell development and leukemogenesis is not known. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ~50% of peripheral blood CLL cases lacking gene mutations. We identify a ‘NOTCH1 CLL gene expression signature’ in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival and signal transduction physiology. In particular, we show that MYC is a direct target of NOTCH1 via B-cell specific distal regulatory elements, thus implicating this oncogene in the pathogenesis of the disease. Overall design: RNA-Seq analysis
Publication Title
Common nonmutational <i>NOTCH1</i> activation in chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Caenorhabditis elegans
- 52 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the presence of extensive, transcriptionally controlled oscillations in the C. elegans, developmental transcriptome. Furthermore, using ribosome profiling, we show that these oscillating transcripts are actively translated. Overall design: Examination of three timecourses that were collected over C. elegans development and analyzed by RNA-seq of mRNA libraries
Publication Title
Extensive oscillatory gene expression during C. elegans larval development.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 34 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the presence of extensive, transcriptionally controlled oscillations in the C. elegans, developmental transcriptome. Furthermore, using ribosome profiling, we show that these oscillating transcripts are actively translated. Overall design: Examination of two timecourses that were collected over C. elegans development and analyzed by RNA-seq of "RiboMinus" libraries
Publication Title
Extensive oscillatory gene expression during C. elegans larval development.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Relative contribution of sequence and structural features to the mRNA-binding of Argonaute/miRNA complexes and the degradation of miRNA targets
Publication Title
Relative contribution of sequence and structure features to the mRNA binding of Argonaute/EIF2C-miRNA complexes and the degradation of miRNA targets.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
microRNAs (miRNAs) constitute a class of small non-coding RNAs (~22nt). They are thought to be generally stable with half-lives of many hours or even days. However, several miRNAs have been reported to decay rapidly in specific situations. In order to examine miRNA stability on a global scale, we quantify relative decay rates of miRNA in first larval stage C. elegans worms that are treated with a transcription inhibitor alpha-amanitin by deep sequencing. Several miRNAs including members of the miR-35 and miR-51 families exhibit accelerated decay. Moreover, biogenesis of miRNAs involves generation of a miRNA duplex intermediate consisting of the miRNA guide strand (miR) and the miRNA passenger strand (miR*). miR and miR* names were originally assigned based on the relative abundance of each strand, with the less abundant strand presumed to be inactive, and thus the miR*. However, subsequent research showed that at least individual miR*s can have biological activity. Our sequencing data reveal that miR*s, operationally defined on the basis of their relative abundance at time point t=1h, are substantially less stable than miRs. This would appear to support the notion that miR*s mainly constitute processing byproducts rather than a less abundant class of functional miRNAs. Overall design: Examination of microRNA decay rates in the first larval stage C. elegans worms.
Publication Title
Engineering of a conditional allele reveals multiple roles of XRN2 in Caenorhabditis elegans development and substrate specificity in microRNA turnover.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We identify mammalian TRIM71 as repressor of mRNAs that inhibits translation and affects mRNA stability.
Publication Title
The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We identify mammalian TRIM71 as repressor of mRNAs that inhibits translation and affects mRNA stability. In this data set we compare the expression profile of mouse ES upon Trim71 KD versus that of the parental cells.
Publication Title
The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Among B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo-1 cell line. Low-level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.
Publication Title
Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 50 Downloadable Samples
- Illumina HiSeq 2000
Description
We perform RNA sequencing and ribosome profiling time course experiments to examine the effect of fully dysregulating all let-7 targets (in let-7(n2853) animals), partially dysregulating only LIN41 (in lin-41(xe11) animals) or fully dysregulating all let-7 targets while partially dysregulating LIN41 in lin-41(xe11); let-7(n2853) double mutant animals. We conclude that effects on gene expression in let-7 mutant animals are largely and quantitatively explained by dysregulation of LIN41 as its primary target. Furthermore, we identify direct LIN41 target genes regulated on the level of translation or mRNA abundance. Overall design: Total RNA-sequencing time course experiments sampling synchronized worm populations of different genetic backgrounds every two hours over the course of development from late L2/early L3 stage to late L4/Young adult stage.
Publication Title
LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms.
Sample Metadata Fields
Cell line, Subject
View Samples