CircRNA-protein complexes: IMP3 protein component defines subfamily of circRNPs

Schneider, Tim; Hung, Lee-Hsueh; Schreiner, Silke; Starke, Stefan; Eckhof, Heinrich; Roßbach, Oliver; Reich, Stefan; Medenbach, Jan; Bindereif, Albrecht

doi:10.1038/srep31313

Cited by 135 publications

(123 citation statements)

References 30 publications

(39 reference statements)

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“…In a recent study our group could provide biochemical evidence for distinct cytoplasmic circRNA-protein complexes in mammalian cells [28]. Since the anucleated platelets represent a very special system without active transcription, we analysed whether circRNAs in platelets are organised as circRNPs (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

Selective release of circRNAs in platelet‐derived extracellular vesicles

Preußer

Hung

Schneider

et al. 2018

J of Extracellular Vesicle

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192

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Circular RNAs (circRNAs) are a novel class of noncoding RNAs present in all eukaryotic cells investigated so far and generated by a special mode of alternative splicing of pre-mRNAs. Thereby, single exons, or multiple adjacent and spliced exons, are released in a circular form. CircRNAs are cell-type specifically expressed, are unusually stable, and can be found in various body fluids such as blood and saliva. Here we analysed circRNAs and the corresponding linear splice isoforms from human platelets, where circRNAs are particularly abundant, compared with other hematopoietic cell types. In addition, we isolated extracellular vesicles from purified and in vitro activated human platelets, using density-gradient centrifugation, followed by RNA-seq analysis for circRNA detection. We could demonstrate that circRNAs are packaged and released within both types of vesicles (microvesicles and exosomes) derived from platelets. Interestingly, we observed a selective release of circRNAs into the vesicles, suggesting a specific sorting mechanism. In sum, circRNAs represent yet another class of extracellular RNAs that circulate in the body and may be involved in signalling pathways. Since platelets are essential for central physiological processes such as haemostasis, wound healing, inflammation and cancer metastasis, these findings should greatly extend the potential of circRNAs as prognostic and diagnostic biomarkers.

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Section: Resultsmentioning

confidence: 99%

Selective release of circRNAs in platelet‐derived extracellular vesicles

Preußer

Hung

Schneider

et al. 2018

J of Extracellular Vesicle

Self Cite

192

145

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“…Are we definitively convinced? It should be noted that this issue was recently also addressed in other studies, based on small subsets of abundant human circRNAs and polysome gradients [10,11], on global analysis of ribosomefootprinting data from human U2OS cells [12], and on polysome fractionation combined with RNA-seq in mouse brain [13]. These studies came to a negative answer and leave us with a controversial impression.…”

mentioning

confidence: 89%

Circular RNAs: Coding or noncoding?

Schneider

Bindereif

2017

Cell Res

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“…Additionally, circFoxo3 was found to interact with CDK2 and p21 to repress cell cycle progression in cancer cell lines (27) and to promote cardiac senescence by interacting with ID-1, E2F1, FAK, and HIF1α in the mammalian heart (28) . Another study showed that a specific RBP, IGF2BP3, associates with several circRNAs (29) .…”

Section: Introductionmentioning

confidence: 99%

Transcriptome-wide profiles of circular RNA and RNA binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression

Okholm

Sathe

Park

et al. 2020

Preprint

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Circular RNAs (circRNAs) are stable, often highly expressed RNA transcripts with potential to modulate other regulatory RNAs. A few circRNAs have been shown to bind RNA binding proteins (RBPs), however, little is known about the prevalence and strength of these interactions in different biological contexts. Here, we comprehensively evaluate the interplay between circRNAs and RBPs in the ENCODE cell lines, HepG2 and K562, by profiling the expression of circRNAs in fractionated total RNA-sequencing samples and analyzing binding sites of 150 RBPs in large eCLIP data sets. We show that KHSRP binding sites are enriched in flanking introns of circRNAs in both HepG2 and K562 cells, and that KHSRP depletion affects circRNA biogenesis. Additionally, we show that exons forming circRNAs are generally enriched with RBP binding sites compared to non-circularizing exons. To detect individual circRNAs with regulatory potency, we computationally identify circRNAs that are highly covered by RBP binding sites and experimentally validate circRNA-RBP interactions by RNA immunoprecipitations. We characterize circCDYL, a highly expressed circRNA with clinical and functional implications in bladder cancer, which is covered with GRWD1 binding sites. We confirm that circCDYL binds GRWD1 in vivo and functionally characterizes the effect of circCDYL-GRWD1 interactions on target genes in HepG2. Furthermore, we confirm interactions between circCDYL and RBPs in bladder cancer cells and demonstrate that circCDYL depletion affects hallmarks of cancer and perturbs the expression of key cancer genes, e.g. TP53 and MYC . Finally, we show that elevated levels of highly RBP-covered circRNAs, including circCDYL, are associated with overall survival of bladder cancer patients. Our study demonstrates transcriptome-wide and cell-type-specific circRNA-RBP interactions that could play important regulatory roles in tumorigenesis.

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CircRNA-protein complexes: IMP3 protein component defines subfamily of circRNPs

Cited by 135 publications

References 30 publications

Selective release of circRNAs in platelet‐derived extracellular vesicles

Selective release of circRNAs in platelet‐derived extracellular vesicles

Circular RNAs: Coding or noncoding?

Transcriptome-wide profiles of circular RNA and RNA binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression

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