Although recent evidence suggests that overlapping sense/antisense transcription is a common feature in higher eukaryotes, the possibility that overlapping transcripts could interact to each other and bear a specific biological function has not been explored. Here we show that a plethora of sense/antisense transcript pairs are co-expressed from 8q24.21 within the same cell and acquire a stable double-stranded RNA conformation. Interestingly, these molecules display predominantly nuclear localization and establish specific interactions with nuclear components. A detailed characterization of a particular sense/antisense pair (ndsRNA-2a) revealed that this molecule displays differential localization throughout the cell cycle, interacts with RCC1 and RAN and through the latter with the mitotic RANGAP1-SUMO1/RANBP2 complex. Notably, an increased number of bi/multi-nucleated cells and chromatin bridges were observed upon ndsRNA-2a overexpression, whereas strand-specific ndsRNA-2a knockdown leads to mitotic catastrophe and cell death. This suggests a functional role of ndsRNA-2a in cell cycle progression that critically requires its double stranded nature. Finally, the identification of hundreds of sense/antisense transcripts pairs harboring ndsRNA profile signatures and their regulation by cellular cues suggests that ndsRNAs constitute a novel class of regulatory molecules that are likely to be involved in a plethora of biological processes. Overall design: PLB985 long (3x datasets) and small (3x datasets) strand specific RNA-Seq for captured RNAs. Global PLB985 for long (2x datasets) and small RNAs (2x datasets). Global libraries for EtOH (vehicle) treated (1x dataset) or retinoic acid induced differentiated PLB985 cells (1x dataset).
Human cells contain natural double-stranded RNAs with potential regulatory functions.
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View SamplesHuman toxicogenomic studies to date have been of limited size, have mainly addressed exposures at the upper end of typical ranges of human exposure, and have often lacked precise, individual estimates of exposure. Previously, we identified genes associated with exposure to high (>10 ppm) levels of the leukemogen, benzene, through transcriptomic analyses of blood cells from small numbers of occupationally exposed workers. Here, we have expanded the study to 125 workers exposed to a wide range of benzene levels, including <1 ppm. Study design, and analysis with a mixed effects model, removed sources of biological and experimental variability and revealed highly significant widespread perturbation of gene expression at all exposure levels. Benzene is an established cause of acute myeloid leukemia (AML), and may cause one or more lymphoid malignancies in humans. Interestingly, acute myeloid leukemia was among the most significant pathways impacted by benzene exposure in the present study. Further, at most exposure levels, immune response pathways including T cell receptor signaling, B cell receptor signaling, and Toll like receptor signaling were impacted, providing support for the biological plausibility of an association between lymphoma and benzene exposure. We also identified a 16-gene expression signature modified by all levels of benzene exposure, comprising genes with roles in immune response, inflammatory response, cell adhesion, cell-matrix adhesion, and blood coagulation. Overall, these findings support, and expand upon, our current understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia and lymphoma. Furthermore, this study shows that with good study design and analysis, transcriptome profiling of the blood of chemically-exposed humans can identify relevant biomarkers across a range of exposures and inform about potential associations with disease risks.
Global gene expression profiling of a population exposed to a range of benzene levels.
Sex, Age, Subject
View SamplesIn theses experimetns we have analized the differential gene expression profile in human trabecular meshwork cells phagocytically challenged to E. coli and pigment under physiological and oxidative stress conditions using affymetrix microarrays
Up-regulated expression of extracellular matrix remodeling genes in phagocytically challenged trabecular meshwork cells.
Specimen part
View SamplesThe transmission of information about the photic environment to the circadian clock involves a complex array of neurotransmitters, receptors, and second messenger systems. Using laser capture microscopy and microarray analysis, a population of genes rapidly induced by light in the suprachiasmatic nucleus is identified.
Identification of novel light-induced genes in the suprachiasmatic nucleus.
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View SamplesIn this study, we examined transcriptional profiles from 3 different microarray platforms, across 103 peripheral blood samples with and without acute rejection, to find a critical gene-set for the diagnosis of acute renal rejection that matched biopsy diagnosis, irrespective of patient demographics, clinical confounders, concomitant infection, immunosuppression usage or sample processing methods. We hypothesized that changes in peripheral blood expression profiles correlate with biopsy-proven rejection, and that these changes could be used as biomarkers for the diagnosis and prediction of acute rejection.
A peripheral blood diagnostic test for acute rejection in renal transplantation.
Disease, Disease stage
View SamplesIn this study, we examined transcriptional profiles from 3 different microarray platforms, across 103 peripheral blood samples with and without acute rejection, to find a critical gene-set for the diagnosis of acute renal rejection that matched biopsy diagnosis, irrespective of patient demographics, clinical confounders, concomitant infection, immunosuppression usage or sample processing methods. We hypothesized that changes in peripheral blood expression profiles correlate with biopsy-proven rejection, and that these changes could be used as biomarkers for the diagnosis and prediction of acute rejection.
A peripheral blood diagnostic test for acute rejection in renal transplantation.
Disease, Disease stage
View SamplesDetermination of gene expression changes in hindlimb muscle (gastrocnemius/soleus) of mdx (dystrophin-deficient) mice at postnatal ages 7, 14, 23, 28, 56, and 112.
Dissection of temporal gene expression signatures of affected and spared muscle groups in dystrophin-deficient (mdx) mice.
No sample metadata fields
View SamplesAn important component of time course microarray studies is the identification of genes that demonstrate significant time-dependent variation in their expression levels. Until recently available methods for performing such significance tests required replicates of individual time points. This paper describes a replicate-free method that was developed as part of a study of the estrous cycle in the rat mammary gland in which no replicate data was collected.
Identifying significant temporal variation in time course microarray data without replicates.
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View SamplesDetermination of gene expression changes in extraocular muscle of mdx (dystrophin-deficient) mice at postnatal ages 14, 28, 56, and 112 days. 3 independent replicates/age/strain.
Dissection of temporal gene expression signatures of affected and spared muscle groups in dystrophin-deficient (mdx) mice.
No sample metadata fields
View SamplesRhesus monkey extraocular muscle. Data set includes: (a) whole medial and lateral rectus muscle and (b) global and orbital muscle layers separately microdissected using a Leica LSM. All samples were expression profiled here using the Affymetrix human U133 A&B arrays. Data form part of publication: Investigative Ophthalmology and Visual Science 45, 2004.
Genome-wide transcriptional profiles are consistent with functional specialization of the extraocular muscle layers.
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