Evolutionary dynamics of circular RNAs in primates

Santos-Rodriguez, Gabriela; Voineagu, Irina; Weatheritt, Robert J.

doi:10.7554/elife.69148

Cited by 24 publications

(9 citation statements)

References 76 publications

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“…This study also highlights that for these genes, the priority might be circRNA production to limit parental gene expression, rather than the exact exon content of the produced circRNAs. [32; 48].…”

Section: Resultsmentioning

confidence: 99%

Polyadenylated RNA sequencing analysis helps establish a reliable catalog of circular RNAs – a bovine example

Robic,

Hadlich,

Monteiro Moreira

et al. 2024

Preprint

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The aim of this study was to compare the circular transcriptome of divergent tissues in order to understand: i) the presence of circular RNAs (circRNAs) that are not exonic circRNAs, i.e. originated from backsplicing involving known exons and, ii) the origin of artificial circRNA (artif_circRNA), i.e. circRNA not generated in-vivo. CircRNA identification is mostly an in-silico process, and the analysis of data from the BovReg project (https://www.bovreg.eu/) provided an opportunity to explore new ways to identify reliable circRNAs. By considering 117 tissue samples, we characterized 23,926 exonic circRNAs, 337 circRNAs from 273 introns (191 ciRNAs, 146 intron circles), 108 circRNAs from small non-coding genes and nearly 36.6K circRNAs classified as other_circRNAs. We suggested in-vivo copying of specific exonic circRNAs by an RNA-dependent RNA polymerase (RdRP) to explain the 20 identified circRNAs with reverse-complement exons. Furthermore, for 63 of those samples we analyzed in parallel data from total-RNAseq (ribosomal RNAs depleted prior to library preparation) with paired mRNAseq (library prepared with poly(A)-selected RNAs). The high number of circRNAs detected in mRNAseq, and the significant number of novel circRNAs, mainly other_circRNAs, led us to consider all circRNAs detected in mRNAseq as artificial. This study provided evidence that there were 189 false entries in the list of exonic circRNAs: 103 artif_circRNAs identified through comparison of total-RNAseq/mRNAseq using two circRNA tools, 26 probable artif_circRNAs, and 65 identified through deep annotation analysis. This study demonstrates the effectiveness of a panel of highly expressed exonic circRNAs (5-8%) in analyzing the diversity of the bovine circular transcriptome.

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Section: Resultsmentioning

confidence: 99%

Polyadenylated RNA sequencing analysis helps establish a reliable catalog of circular RNAs – a bovine example

Robic,

Hadlich,

Monteiro Moreira

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The low expression levels, the shared sequence identity of circRNAs with their cognate linear mRNAs, and the fact that they can only be detected via the backsplice junction reads makes detection and quantification challenging. Though several bioinformatic detection tools have been developed as well as the enrichment of circRNAs after RNAse digestion, the detection and quantification of circRNAs still suffers from low accuracy and high false-positive rates [ 55 , 56 ]. In our study, we used seekCRIT [ 18 ], a computational tool that identifies all transcripts, including circRNAs, from high, in-depth sequencing of ribosomal-depleted RNA.…”

Section: Discussionmentioning

confidence: 99%

PARP1 Regulates Circular RNA Biogenesis though Control of Transcriptional Dynamics

Eleazer

Silva

Andreeva

et al. 2023

Cells

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Circular RNAs (circRNAs) are a recently discovered class of RNAs derived from protein-coding genes that have important biological and pathological roles. They are formed through backsplicing during co-transcriptional alternative splicing; however, the unified mechanism that accounts for backsplicing decisions remains unclear. Factors that regulate the transcriptional timing and spatial organization of pre-mRNA, including RNAPII kinetics, the availability of splicing factors, and features of gene architecture, have been shown to influence backsplicing decisions. Poly (ADP-ribose) polymerase I (PARP1) regulates alternative splicing through both its presence on chromatin as well as its PARylation activity. However, no studies have investigated PARP1’s possible role in regulating circRNA biogenesis. Here, we hypothesized that PARP1’s role in splicing extends to circRNA biogenesis. Our results identify many unique circRNAs in PARP1 depletion and PARylation-inhibited conditions compared to the wild type. We found that while all genes producing circRNAs share gene architecture features common to circRNA host genes, genes producing circRNAs in PARP1 knockdown conditions had longer upstream introns than downstream introns, whereas flanking introns in wild type host genes were symmetrical. Interestingly, we found that the behavior of PARP1 in regulating RNAPII pausing is distinct between these two classes of host genes. We conclude that the PARP1 pausing of RNAPII works within the context of gene architecture to regulate transcriptional kinetics, and therefore circRNA biogenesis. Furthermore, this regulation of PARP1 within host genes acts to fine tune their transcriptional output with implications in gene function.

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“…Our study provides a comprehensive profile of circRNA expression in a human model of neuronal differentiation. Although previous reports have suggested high conservation of circRNAs, more recent evidence indicates that circRNA exons exhibit similar conservation to neighbouring linear exons and that the majority of circRNAs are species-specific with only ∼20% of mouse circRNAs having human homologs (Gruhl et al , 2021; Guo et al ., 2014; Santos-Rodriguez et al , 2021). Exploring circRNA expression and function within a human-genetic context is therefore critical to understanding the role of circRNAs in both disease and normal brain development.…”

Section: Discussionmentioning

confidence: 99%

Circular RNAs arising from synaptic host genes are modulated by SFPQ RNA-binding protein and increased during human neuronal differentiation

Watts

Oksanen

Lejerkrans

et al. 2022

Preprint

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Circular RNAs (circRNAs) are emerging as a key component of the complex neural transcriptome implicated in brain development. However, the specific expression patterns and functions of circRNAs in human neuronal differentiation have not been explored. Using total RNA sequencing analysis, we identified expressed circRNAs during the differentiation of human neuroepithelial stem (NES) cells into developing neurons and discovered that many circRNAs originated from host genes with synaptic functions. Interestingly, when assessing population data and rare de novo variants in autism spectrum disorder (ASD) candidate host genes, exons giving rise to circRNAs had a significantly higher frequency of genetic variants. Screening for RNA-binding protein sites identified enrichment of Splicing Factor Proline and Glutamine Rich (SFPQ) motifs in increased circRNAs, several of which we validated as being reduced by SFPQ knockdown and enriched in SFPQ ribonucleoprotein complexes. Our study provides an in-depth characterisation of circRNAs in a human neuronal differentiation model and highlights SFPQ as both a regulator and binding partner of circRNAs elevated during neuronal maturation.

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Evolutionary dynamics of circular RNAs in primates

Cited by 24 publications

References 76 publications

Polyadenylated RNA sequencing analysis helps establish a reliable catalog of circular RNAs – a bovine example

Polyadenylated RNA sequencing analysis helps establish a reliable catalog of circular RNAs – a bovine example

PARP1 Regulates Circular RNA Biogenesis though Control of Transcriptional Dynamics

Circular RNAs arising from synaptic host genes are modulated by SFPQ RNA-binding protein and increased during human neuronal differentiation

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