Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The RNA-binding protein SFPQ preserves long-intron splicing and regulates circRNA biogenesis

ABSTRACT: Circular RNAs (circRNAs) represent an abundant and conserved entity of non-coding RNAs, however the principles of biogenesis are currently not fully understood. To elucidate features important for circRNA production, we performed global analyses of RNA-binding proteins associating with the flanking introns of circRNAs, and we identified two factors, SFPQ and NONO, to be highly enriched with circRNAs. We observe a subclass of circRNAs, coined DALI circRNAs, with distal inverted Alu elements and long introns to be highly deregulated upon SFPQ knockdown. Moreover, SFPQ depletion leads to increased intron retention with concomitant induction of cryptic splicing prevalent for long introns causing in some cases premature transcription termination and polyadenylation. Aberrant splicing in the upstream and downstream regions of circRNA producing exons are critical for shaping the circRNAome, and specifically, we identify a conserved impact of missplicing in the immediate upstream region to drive circRNA biogenesis. Collectively, our data show that SFPQ plays an important role in maintaining intron integrity by ensuring accurate splicing of long introns, and disclose novel features governing Alu-independent circRNA production.

ORGANISM(S): Homo sapiens

PROVIDER: GSE157622 | GEO | 2020/09/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals

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

Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals

2015-01-06 | GSE63823 | GEO

The RNA-binding protein SFPQ preserves long-intron splicing and regulates circRNA biogenesis

Project description:The RNA-binding protein SFPQ preserves long-intron splicing and regulates circRNA biogenesis

| PRJNA662248 | ENA

Sensing self and nonself circular RNAs

Project description:Circular RNAs (circRNAs) are single-stranded RNAs that are joined head to tail. Initially discovered as pathogen genomes such as hepatitis D virus (HDV) and plant viroids, circRNAs are recently recognized as a pervasive class of noncoding RNAs in eukaryotic cells, generated through back splicing. circRNAs have been postulated to function in cell-to-cell information transfer or memory due to their extraordinary stability. Whether and how circRNAs trigger immune recognition is not known. Here we show that exogenous circular RNAs potently stimulate immune signaling, and mammalian cells sense self vs. nonself circRNAs via circRNA biogenesis. Transfection of purified in vitro spliced circRNA into mammalian cells led to potent induction of innate immunity genes. The nucleic acid sensor RIG-I is necessary and sufficient to sense foreign circRNA, and RIG-I and foreign circRNA co-aggregate in cytoplasmic foci. CircRNA activation of innate immunity is independent of 5’ triphosphate, double-stranded RNA structure, or primary sequence of the foreign circRNA. Instead, self-nonself discrimination depends on the intron that programs the circRNA. Use of a human intron to express a foreign circRNA sequence abrogates immune activation, and the mature human circRNA is associated with diverse RNA binding proteins reflecting its endogenous splicing and biogenesis. These results reveal innate immune sensing of circRNA, a prevalent class of host and pathogen RNAs, and highlight introns—the predominant output of mammalian transcription—as unexpected arbiters of self-nonself identity in the RNA world.

2017-06-29 | GSE81345 | GEO

Genome-wide identification of cancer-specific alternative splicing in circRNA

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

High-throughput sequencing in HNRNPD knock-out and knock-in HEK293T cell lines

Project description:As HNRNPD regulates the alternative splicing of hundreds of genes, we sought to investigate whether HNRNPD could regulate the biogenesis of circRNAs. To identify the effect of HNRNPD on circRNAs and linear RNAs, we performed circRNA and linear RNAs (ployA enrichment RNA and lncRNA) sequencing in HNRNPD knockout and wild-type HEK293T cells. We also inserted 3FHBH (3xFLAG, Histidine, Biotin, and Histidine) into the HNRNPD genome to obtain HEK293T_HNRNPD_3FHBH cells by using CRISPR-Cas9 technology, which was used to ascertain the direct HNRNPD targeting RNA sequence with the help of FLASH sequencing (Fast Ligation of RNA after some sort of Affinity Purification for High-throughput Sequencing). To evaluate the impacts of HNRNPD deficiency on circRNA formation, we captured nascent RNA in HEK293T and HNRNPD knock-out HEK293T cells by immunoprecipitation of 5-ethyluridine (EU) labeling. Comparative analysis of these data, we found the higher propensity of binding to introns of HNRNPD was related to inhibiting circRNA biogenesis.

2023-09-30 | GSE212767 | GEO

High-throughput sequencing in HNRNPD knock-out SW839 cell lines

Project description:As HNRNPD regulates the alternative splicing of hundreds of genes, we sought to investigate whether HNRNPD could regulate the biogenesis of circRNAs. To identify the effect of HNRNPD on circRNAs, we performed circRNA sequencing in HNRNPD knockout and wild-type SW839 cells. In addition, to evaluate the impacts of HNRNPD deficiency on circRNA formation, we captured nascent RNA in SW839 and HNRNPD knock-out SW839 cells by immunoprecipitation of 5-ethyluridine (EU) labeling. Comparative analysis of these data, we found the higher expression level of circRNAs in HNRNPD KO SW839 cells.The HNRNPD could influence the circRNA biogenesis.

2024-01-01 | GSE240942 | GEO

Profiling lariat intermediates reveals genetic determinants of early and late co-transcriptional splicing

Project description:Long introns with short exons in vertebrate genes are thought to require spliceosome assembly across exons (exon definition), rather than introns, thereby requiring transcription of an exon to splice an upstream intron. Here, we developed CoLa-seq (co-transcriptional lariat sequencing) to investigate the timing and determinants of co-transcriptional splicing genome wide. Unexpectedly, 90% of all introns, including long introns, can splice before transcription of a downstream exon, indicating that exon definition is not obligatory for most human introns. Still, splicing timing varies dramatically across introns, and various genetic elements determine this variation. Strong U2AF2 binding to the polypyrimidine tract predicts early splicing, explaining exon definition-independent splicing. Together, our findings question the essentiality of exon definition and reveal features beyond intron and exon length that are determinative for splicing timing.

2022-11-26 | GSE204834 | GEO

Systematic identification and characterization of Exon-intron circRNAs

Project description:Exon-intron circRNA (EIciRNA) is a subclass of backsplicing-generated circRNAs featured with intron retention, among which some play roles in transcriptional regulation. We aim to characterize EIciRNAs by developing pipeline and investigate the factors involved in regulating EIciRNA biogenesis using CRISPR-Cas9 screen, as well as the physiology functions of EIciRNAs during neuronal differentiation.

2024-03-04 | GSE253233 | GEO