Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33772 | GEO | 2012/02/10
SECONDARY ACCESSION(S): PRJNA148385
REPOSITORIES: GEO
Similar Datasets
Project description:Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence. By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order. Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs. Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a widespread and perhaps general feature of the gene expression program in human cells. 3 samples of non-malignant primary human leukocytes, one replicate each
2012-02-10 | E-GEOD-33772 | biostudies-arrayexpress
Project description:In order to find out circular RNAs profiles in human bladder cancer tissues and normal bladder tissues, we characterized circuclar RNA transcripts by performing RNA-Seq on ribosomal RNA-depleted total RNA from three pairs of human bladder cancer tissues and paired normal bladder tissues.A computational pipeline based on the anchor alignment of unmapped reads was used to identify circular RNAs. Collectively, we identified16,535 distict circular RNAs, most of them origined from exons (88.96%), others from introns, linc RNA, intergenic region, 3’UTR and 5’UTR. Among all these circRNAs, 571 circRNAs were differentially expressed between bladder cancer tissues and normal bladder tissues, and 524 circRNAs were downregulated in bladder cancer tissues (91.2%), others were upreguluated. These significantly differential expressed circular RNA might have regulatory function in bladder cancer, and worth to be further explored.
2017-08-04 | GSE97239 | GEO
Project description:The pervasive expression of circular RNA from protein coding loci is a recently discovered feature of many eukaryotic gene expression programs. Computational methods to discover and quantify circular RNA are essential to the study of the mechanisms of circular RNA biogenesis and potential functional roles they may play. In this paper, we present a new statistical algorithm that increases the sensitivity and specificity of circular RNA detection.by discovering and quantifying circular and linear RNA splicing events at both annotated exon boundaries and in un-annotated regions of the genome Unlike previous approaches which rely on heuristics like read count and homology between exons predicted to be circularized to determine confidence in prediction of circular RNA expression, our algorithm is a statistical approach. We have used this algorithm to discover general induction of circular RNAs in many tissues during human fetal development. We find that some regions of the brain show marked enrichment for genes where circular RNA is the dominant isoform. Beyond this global trend, specific circular RNAs are tissue specifically induced during fetal development, including a circular isoform of NCX1 in the developing fetal heart that, by 20 weeks, is more highly expressed than the linear isoform as well as beta-actin. In addition, while the vast majority of circular RNA production occurs at canonical U2 (major spliceosome) splice sites, we find the first examples of developmentally induced circular RNAs processed by the U12 (minor) spliceosome, and an enriched propensity of U12 donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, our algorithm and its results suggest a potentially significant role for circular RNA in human development. 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA with Ribo-Zero Gold sample prep kit.
2015-06-25 | E-GEOD-64283 | biostudies-arrayexpress
Project description:The study aimed to identify circular RNAs (circRNAs) commonly back-spliced to intronic region of different sets of endothelial cells (human cardiac microvascular endothelial cells (HCMEC), human aortic endothelial cells (HAoEC), human umbilical vein endothelial cells (HUVECs)) and to evaluate their overall expression and their expression compared to their respective host gene. Identified circRNAs were quality controlled by their detection in an additional exonuclease RNase R treated RNA-Seq dataset performed with RNA of HUVECs. CircRNAs were compared for overlapping detection between datasets and filtered by annotation for circRNAs back-spliced to intronic regions. Common endothelial intronic circRNAs candidates were compared to respective murine circRNAs stored in the circATLAS database. The prime candidate cZNF292 was functionally characterized in vivo and in vitro.
2023-11-30 | E-MTAB-11171 | biostudies-arrayexpress
Project description:We have used RNA-seq to examine circular RNAs from poly(A)-/ribo- RNAs in human and mouse embryonic stem cells In order to identify novel circular RNAs from different species
2014-08-19 | E-GEOD-60467 | biostudies-arrayexpress
Project description:Alternative splicing of mRNA diversifies the function of human proteins, with tissue- and cell-specific protein isoforms being the most difficult to validate. While transcriptomic experiments enable the detection of many alternatively spliced transcripts, it is not known if these transcripts have protein-coding potential. We recently published the PG Nexus pipeline, which facilitates high confidence validation of exons and exon-exon junctions of spliced transcripts by integrating transcriptomics and proteomics data. Using the PG Nexus, we analyzed undifferentiated human mesenchymal stem cells and compared the number of protein isoforms validated using different protein sequence database, including public online databases and RNA-seq derived databases. With significant overlaps with other databases, we identified 8,011 exons and 3,824 splice junctions with the Ensembl database. Both exonic and junction peptides were important for protein isoform validation. The Ensembl database consistently outperformed the other data sources, but predicted open reading frames from RNA-seq derived transcripts were comparable, with only 6 less splice junctions validated. Using proteotypic and isoform-specific peptides, we validated 462 protein isoforms. This number increases to 1,083 if multiple proteotypic peptides per protein are included. Multiplexing proteotypic peptides in SRM assays or similar experiments will increase the confidence and coverage of protein isoform validation experiments.
2015-05-20 | PXD001449 | Pride
Project description:In most plants, centromeric DNA contains highly repetitive sequences, including tandem repeats and retrotransposons; however, the roles of these sequences in the structure and function of the centromere are unclear. Here, we found that retrotransposon-derived back-spliced RNA can bind to the centromere through R-loops and regulate the formation of centromeric chromatin loops. Multiple RNA sequences from centromeric retrotransposons (CRMs) were enriched in maize (Zea mays) centromeres and back spliced RNA from CRM1 were detected. We identified three types of circular CRM1 RNAs with the same back-splicing site based on the back-spliced sequences. These circular RNAs bound to the centromere through R-loops. Two R-loop sites inside a single circular RNA promoted the formation of chromatin loops in CRM1 regions. When RNAi was used to target the back-spliced site of the circular CRM1 RNAs, the levels of R-loops and chromatin loops formed by these circular RNAs decreased, while the levels of R-loops produced by linear RNAs with similar binding sites increased. Linear RNAs with only one R-loop site could not promote chromatin loop formation. Higher levels of R-loops and lower levels of chromatin loops in the CRM1 regions of RNAi plants led to a reduced localization of the centromeric H3 variant (CENH3). Our work reveals that centromeric chromatin organization by circular CRM1 RNAs via R-loops and chromatin loops. R-loops are integral components of centromeric chromatin. Proper centromere structure is essential for CENH3 localization. CRM1 elements may have helped to build a suitable chromatin environment during centromere evolution.
2020-01-01 | GSE137701 | GEO
Project description:<p>Few genetic drivers of children with hyperdiploid precursor B-cell acute lymphoblastic leukemia (ALL) have been identified to date. In an effort to detect novel genomic rearrangements that could be promoting leukemogenesis in this subset of patients, we sequenced ribosomal RNA-depleted transcriptomes isolated from 5 hyperdiploid acute lymphoblastic leukemia samples. In addition to looking for novel genomic rearrangements, we also sought to identify transcripts that could be created as a result of a novel posttranscriptional process. Surprisingly, we identified transcripts created as the result of exon circularization. The results of our studies are present in the paper "Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types" published in PLoS ONE (PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/22319583" target="_blank">22319583</a>).</p>
| phs000522 | dbGaP
Project description:Transcripts from the human and mouse CAPN10 cDNA sequences cloned into pcDNA and expressed in cultured cells undergo unexpected splicing. Peptide sequences missing from the spliced version of CAPN10 expressed in COS7 cells were determined by MS analysis.
2022-01-01 | PXD026551 | JPOST Repository
Project description:Human genes have numerous exons that are differentially spliced within pre-mRNA. Understanding how multiple splicing events are coordinated across nascent transcripts requires quantitative analyses of transient RNA processing events in living cells. We developed nanopore analysis of CO-transcriptional Processing (nano-COP), in which nascent RNAs are directly sequenced through nanopores, exposing the dynamics and patterns of RNA splicing without biases introduced by amplification. nano-COP showed that in both human and Drosophila cells, co-transcriptional splicing occurs after RNA polymerase II transcribes several kilobases of pre-mRNA, suggesting that metazoan splicing transpires distally from the transcription machinery. Inhibition of the branch site recognition complex SF3B globally abolished co-transcriptional splicing in both species. Our findings revealed that splicing order does not strictly follow the order of transcription and is influenced by cis-regulatory elements. In human cells, introns with delayed splicing frequently neighbor alternative exons and are associated with RNA-binding factors. Moreover, neighboring introns in human cells tend to be spliced concurrently, implying that splicing occurs cooperatively. Thus, nano-COP unveils the organizational complexity of metazoan RNA processing.
2019-12-12 | GSE123191 | GEO