Circular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human Alu repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified new circRNAs in C. elegans. Reverse complementary sequences between introns bracketing circRNAs were significantly enriched compared to linear controls. By scoring the presence of reverse complementary sequences in human introns we predicted and experimentally validated novel circRNAs. We show that introns bracketing circRNAs are highly enriched in RNA editing or hyper-editing events. Knockdown of the double-strand RNA editing ADAR1 enzyme significantly and specifically up-regulated circRNA expression. Together, our data support a model of animal circRNA biogenesis in which competing RNA:RNA interactions of introns form larger structures which promote circularization of embedded exons, while ADAR1 antagonizes circRNA expression by melting stems within these interactions. Thus, we assign a new function to ADAR1. Overall design: Examination of 12 samples in different stages of C.elegans development.
Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals.
Cell line, Treatment, Subject
View SamplesBiomarkers of osteoarthritis (OA) that can accurately diagnose the disease at the earliest stage would significantly support efforts to develop treatments for prevention and early intervention. The different stages of disease progression are described by the complex pattern of transcriptional regulations. The dynamics in pattern alterations were monitored in each individual animal during the time-course of OA progression.
Blood Transcriptional Signatures for Disease Progression in a Rat Model of Osteoarthritis.
Treatment
View SamplesChronic opiate use produces molecular and cellular adaptations in the nervous system, leading to tolerance, physical dependence and addiction. Genome-wide comparison of morphine-induced changes in brain transcription of mouse strains with different opioid-related phenotypes provides an opportunity to discover the relationship between gene expression and behavioral response to the drug.
Morphine effects on striatal transcriptome in mice.
No sample metadata fields
View SamplesDifferences between groups of children with obesity and healthy controls.
Looking for new diagnostic tools and biomarkers of hypertension in obese pediatric patients.
Specimen part, Disease
View SamplesTo identify molecular effects of chronic drug treatment, heroin and methamphetamine treated animals were compared with saline treated animals at multiple time-points using microarray technology. Gene expression profile was assessed 14 h after the last dose of 1, 3, 6 or 12 days drug treatment and after 13, 15, 18 or 24 days of withdrawal.
Common transcriptional effects in the mouse striatum following chronic treatment with heroin and methamphetamine.
Specimen part, Compound
View SamplesChronic exposure to opioids induces adaptations in brain function that lead to the formation of the behavioral and physiological symptoms of drug dependence and addiction.
Behavioral and transcriptional patterns of protracted opioid self-administration in mice.
Specimen part
View SamplesAblation of the Srf gene in dopaminoceptive neurons of the brain was performed using the Cre/loxP system, with the recombinase expressed from a BAC-derived Drd1a promoter.
Loss of the serum response factor in the dopamine system leads to hyperactivity.
No sample metadata fields
View SamplesUsing whole-genome Affymetrix microarrays (HG-U133A), we characterized the transcriptome profile of cultured human macrophages stimulated for 4 h with interleukin 1 (IL-1) or interleukin 6 (IL-6). We found that, in distinction to liver cells, IL-1 is much more potent than IL-6 in modifying macrophage gene expression, although considerable heterogeneity in response of macrophages deriving from individual blood donors was observed. The obtained results permitted to identify a large number of cytokine-responsive genes. coding for proteins of unknown function that are now being studied in our laboratory. They may represent novel targets in the anti-inflammatory therapy.
Identification of interleukin-1 and interleukin-6-responsive genes in human monocyte-derived macrophages using microarrays.
No sample metadata fields
View SamplesIn summary, we characterized genomic signatures of response to drugs of abuse and we found positive correlations between the drug-induced expression and various behavioral effects. These signatures are formed by two dynamically inducible transcriptional networks: (1) CREB/SRF-dependent gene pattern that appears to be related to drug-induced neuronal activity, (2) the pattern of genes controlled at least in part via release of glucocorticoids and androgens that are associated with rewarding and harmful drug effects. The discovery of co-expressed networks of genes allowed for the identification of master-switch controlling factors involved in molecular response to the drugs. Finally, using the pharmacological tools we were able to dissect and inhibit particular gene expression patterns from genomic profile.
The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum.
Compound, Time
View SamplesWe used the CRISPR/Cas9 technique to construct nbr1-KO lines (KO1 and KO3) in order to test the effects of AtNBR1 depletion. Reduced expression of several ABA-up regulated genes were observed in shoots of the two KO lines.
A selective autophagy cargo receptor NBR1 modulates abscisic acid signalling in Arabidopsis thaliana.
Age, Specimen part
View Samples