RNA-seq after KD or OE of circRNAs or linear gene
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE123940 | GEO | 2019/02/07
REPOSITORIES: GEO
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Project description:Standard RNA analyses using microarrays and low-coverage polyadenylation enriched RNA-Sequencing (RNA-Seq) cannot fully characterize the complexity of the cancer transcriptome. To fully elucidate the transcriptome of prostate tumours, we performed ultra-deep total RNA-Seq on 144 localized prostate tumours with long-term clinical follow up. Analysis of linear RNAs identified a transcriptomic subtype associated with the aggressive intraductal carcinoma subhistology, and a fusion gene profile that differentiates localized from metastatic prostate cancers. Analysis of back-splicing events identified widespread RNA circularization, with the average tumour expressing 7,140 distinct circular RNAs. The degree of aberrant circRNA production is correlated to disease progression in multiple clinical cohorts. Loss of function screens identified 11.3% of the screened circRNAs as essential to prostate cancer proliferation, and for 93.6% of these, their parental linear genes are not required for proliferation. Follow-up studies on circCSNK1G3 revealed its role in regulating cell cycle progression. Ultra-deep transcriptome sequencing thus provides a more comprehensive view of the linear and circular transcriptional and functional landscapes of localized prostate cancer.
2019-02-07 | GSE113121 | GEO
Project description:Standard RNA analyses using microarrays and low-coverage polyadenylation enriched RNA-Sequencing (RNA-Seq) cannot fully characterize the complexity of the cancer transcriptome. To fully elucidate the transcriptome of prostate tumours, we performed ultra-deep total RNA-Seq on 144 localized prostate tumours with long-term clinical follow up. Analysis of linear RNAs identified a transcriptomic subtype associated with the aggressive intraductal carcinoma subhistology, and a fusion gene profile that differentiates localized from metastatic prostate cancers. Analysis of back-splicing events identified widespread RNA circularization, with the average tumour expressing 7,140 distinct circular RNAs. The degree of aberrant circRNA production is correlated to disease progression in multiple clinical cohorts. Loss of function screens identified 11.3% of the screened circRNAs as essential to prostate cancer proliferation, and for 93.6% of these, their parental linear genes are not required for proliferation. Follow-up studies on circCSNK1G3 revealed its role in regulating cell cycle progression. Ultra-deep transcriptome sequencing thus provides a more comprehensive view of the linear and circular transcriptional and functional landscapes of localized prostate cancer.
2019-02-07 | GSE113120 | GEO
Project description:Standard RNA analyses using microarrays and low-coverage polyadenylation enriched RNA-Sequencing (RNA-Seq) cannot fully characterize the complexity of the cancer transcriptome. To fully elucidate the transcriptome of prostate tumours, we performed ultra-deep total RNA-Seq on 144 localized prostate tumours with long-term clinical follow up. Analysis of linear RNAs identified a transcriptomic subtype associated with the aggressive intraductal carcinoma subhistology, and a fusion gene profile that differentiates localized from metastatic prostate cancers. Analysis of back-splicing events identified widespread RNA circularization, with the average tumour expressing 7,140 distinct circular RNAs. The degree of aberrant circRNA production is correlated to disease progression in multiple clinical cohorts. Loss of function screens identified 11.3% of the screened circRNAs as essential to prostate cancer proliferation, and for 93.6% of these, their parental linear genes are not required for proliferation. Follow-up studies on circCSNK1G3 revealed its role in regulating cell cycle progression. Ultra-deep transcriptome sequencing thus provides a more comprehensive view of the linear and circular transcriptional and functional landscapes of localized prostate cancer.
2019-02-07 | GSE113119 | GEO
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
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2015-12-17 | E-GEOD-71195 | biostudies-arrayexpress
Project description:The functional contribution of many circular RNAs (circRNAs) to cancer is poorly understood. Here, we report that knockdown in sarcoma cells of the endogenous circRNA, circCsnk1g3, modulates changes in immune cell proportions and expression profiles in the tumor lung microenvironment.
2022-10-20 | GSE163201 | GEO
Project description:Circular RNAs (circRNAs) are widespread circular forms of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of both coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and micro-RNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms only. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes. Histone 3 Lysine 27 Acetylation â 2 replicates
2015-12-17 | E-GEOD-71196 | biostudies-arrayexpress
Project description:Covalently closed circular RNA molecules (circRNAs) have recently emerged as a class of RNA isoforms with widespread and tissue specific expression across animals, oftentimes independent of the corresponding linear mRNAs. circRNAs are remarkably stable and sometimes highly expressed molecules. Here, we sequenced RNA in human peripheral whole blood to determine the potential of circRNAs as biomarkers in an easily accessible body fluid. We report the reproducible detection of thousands of circRNAs. Importantly, we observed that hundreds of circRNAs are much higher expressed than corresponding linear mRNAs. Thus, circRNA expression in human blood reveals and quantifies the activity of hundreds of coding genes not accessible by classical mRNA specific assays. Our findings suggest that circRNAs could be used as biomarker molecules in standard clinical blood samples. Sequencing of blood RNA from five healthy individuals (biological replicates) plus technical replicate of one sample and detection of circRNAs.
2015-10-26 | E-GEOD-73570 | biostudies-arrayexpress
Project description:In platelets, splicing and translation occur in the absence of a nucleus. However, the integrity and stability of mRNAs derived from megakaryocyte progenitor cells remain poorly quantified on a transcriptome-wide level. As circular RNAs (circRNAs) are resistant to degradation by exonucleases, their abundance relative to linear RNAs can be used as a surrogate marker for mRNA stability in the absence of transcription. Here we show that circRNAs are enriched in human platelets 17-188 fold relative to nucleated tissues, and 14-26 fold relative to samples digested with RNAseR to selectively remove linear RNA. We compare RNAseq read depths inside and outside circRNAs to provide in silico evidence of transcript circularity, show that exons within circRNAs are enriched ~13X in platelets relative to nucleated tissues, and identify 3162 genes significantly enriched for circRNAs including some where all RNAs appear to be derived from circular molecules. We also confirm that this is a feature of other anucleate cells through transcriptome sequencing of mature erythrocytes, demonstrate that circRNAs are not enriched in megakaryocytes, and that linear RNAs decay more rapidly than circRNAs in platelet preparations. Collectively, these results suggest that circulating platelets have lost on aveage over 90% of their progenitor mRNAs, and that translation in platelets occurrs against the backdrop of a highly degraded transcriptome. Finally, we find that transcripts classified as products of reverse transcriptase template switching are both enriched in platelets and resistant to decay, countering the recent suggestion that up to 50% of rearranged RNAs are artefacts. A single rRNA depleted total RNA sample was sequenced. This together with 25 publicly available rRNA depleted total RNA samples (including 3 from platelets) were analysed using PTESFinder v 1 (http://sourceforge.net/projects/ptesfinder-v1/) to identify back-splice junctions, characteristic of circRNA transcripts. The contribution of circRNA producing exons was analysed on a gene by gene basis as follows: All circRNA transcripts identified in any sample were first pooled to define exons which can contribute to circRNA generation using custom scripts (available on request). For each sample, expression estimates (RPKMI) across all circRNA producing exons were computed for each locus using the total size of exons (in bp) and the read counts mapping to them. Similarly, total size and exonic read counts for exons for which no circRNA were detected in any sample were used to compute expression estimates (RPKME) for non-circRNA producing exons for each locus. Abundance ratios (RPKMI/RPKME and RPKMI/RPKMI+RPKME) were calculated and compared between Platelets and human tissues using Wilcoxon signed-rank test. Please note that the '25sample_info_accn_no.txt' contains the accession numbers and tissue/cell type information for 25 samples analyzed together.
2015-12-12 | E-GEOD-69192 | biostudies-arrayexpress
Project description:Circular RNAs (circRNAs), which can function as regulators of gene expression, are formed by back-splicing of precursor mRNAs in the nucleus. circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here, we uncover a pathway specific for nuclear export of circular RNA. This pathway requires Ran-GTP, Exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter, CRM1, selectively increases nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Analysis of nuclear circRNA binding proteins reveals that interaction of IGF2BP1 with circRNA is enhanced by Ran-GTP, whereas its interaction with linear RNA is inhibited by Ran-GTP. Depletion or knockout of Exportin-2 specifically inhibits nuclear export of circRNA, while formation of an Exportin-2 circRNA export complex requires Ran-GTP and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Exportin-2 to export circRNAs in a mechanism analogous to protein export, rather than mRNA export.
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