ELAV mediates circular RNA biogenesis in neurons [RIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE268730 | GEO | 2025/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In fly brains, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape.
2025-06-01 | GSE296576 | GEO
Project description:Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In fly brains, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape.
2025-06-01 | GSE268734 | GEO
Project description:Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In fly brains, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape.
2025-06-01 | GSE268733 | GEO
Project description:Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In fly brains, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape.
2025-06-01 | GSE268732 | GEO
Project description:Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In fly brains, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape.
2025-06-01 | GSE268731 | GEO
Project description: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. Examination of 12 samples in different stages of C.elegans development.
2015-01-06 | E-GEOD-63823 | biostudies-arrayexpress
Project description:Circular RNAs (circRNAs) are an endogenous class of animal RNAs. Despite their abundance, their function and expression in the nervous system are unknown. Therefore, we sequenced RNA from different brain regions, primary neurons, isolated synapses, as well as during neuronal differentiation. Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their mRNA isoforms. circRNA expression correlated negatively with expression of the RNA-editing enzyme ADAR1. Knockdown of ADAR1 induced elevated circRNA expression. Together, we provide a circRNA brain expression atlas and evidence for important circRNA functions and values as biomarkers. To assess circRNA expression in mammalian brain, we sequenced and analyzed mouse brain regions (hippocampus, cerebellum, prefrontal cortex and olfactory bulb), various neuronal differentiation (mouse P19 and human SH-SY5Y cells) and maturation (mouse cortical neurons) stages, and subcellular compartments in mouse (synaptoneurosomal fraction, cytoplasmic fraction, whole brain lysate).
2015-04-24 | E-GEOD-65926 | biostudies-arrayexpress
Project description:Circular RNAs (circRNAs), formed by the atypical head-to-tail splicing of exons, have re-emerged as a potentially interesting RNA species given recent reports of a surprising diversity and abundance of circRNA in organisms ranging from worm to human. Here, using deep RNA sequencing, we profiled different RNA species in mouse and observed that circRNAs are significantly enriched in neural tissue, relative to other tissues. Using PacBio sequencing, we determined, for the first time, the circular structure of this population of circRNAs as well as their full-length sequences. We discovered that a disproportionate fraction of the brain circRNA population is derived from host genes that code for synaptic proteins. Moreover, based on the separate profiling of the RNAs localized in neuronal cell bodies and neuropil (enriched in axons and dendrites), we found that, on average, circular RNAs are more enriched in the neuropil than their host gene mRNA isoforms. Using high resolution in situ hybridization we, for the first time, directly visualized circRNA punctae in the dendrites of neurons. The host gene origin and location of the circRNA in neurons suggest the possibility that circRNAs might participate in the regulation of synaptic function and plasticity. Consistent with this idea, we observed via profiling at different developmental stages, that the abundance of many circular RNAs changes abruptly at a time corresponding to synaptogenesis. In addition, following a homeostatic downscaling of neuronal activity many circRNAs exhibit significant up or down-regulation. These data indicate that brain circRNAs are positioned to respond to and regulate synaptic function. Circular RNA profiling in 13 different samples in mice and four samples in rat, using Illumina sequencing
2015-02-25 | E-GEOD-61991 | biostudies-arrayexpress
Project description:Circular RNAs (circRNAs) in animals are an enigmatic class of RNAs with unknown function. To systematically explore circRNAs, we sequenced and computationally analyzed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, with oftentimes tissue/developmental stage specific expression. Sequence analysis suggested important regulatory functions for circRNAs. Indeed, we discovered that human circRNA CDR1as is densely bound by miRNA effector complexes and harbors 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebra fish impaired midbrain development similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, indicating previously unrecognized regulatory potential of coding sequences. 1 Sample
2013-02-28 | E-GEOD-43572 | biostudies-arrayexpress
Project description:Circular RNA (circRNA) is a group of RNA family generated by RNA circularization, which was discovered ubiquitously across different cancers. However, the internal structure of circRNA is hard to be determined since of the alternative splicing happened in exons and introns of circRNA and the cancer-specific alternative splicing of circRNA is less to be identified. Here we proposed a custom tool CircSplice, which could identify internal alternative splicing of circRNA and compare the differential splicing between samples. By applying CircSplice in ccRCC, we identified cancer-specific alternative splicing (AS) events belong to circRNAs in ccRCC. We further confirmed the existence of alternative splicing events in circRNAs by RT-PCR. This study is the first exploration of cancer-specific alternative splicing in circRNAs, which helps researchers to better understand potential functions of splicing of circRNAs in cancers.
2019-03-11 | GSE124453 | GEO