Identifying and Characterizing circRNA-Protein Interaction

Du, William W.; Zhang, Chao; Yang, Weining; Yong, Tianqiao; Awan, Faryal Mehwish; Yang, Burton B.

doi:10.7150/thno.21299

Cited by 476 publications

(349 citation statements)

References 54 publications

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“…Those circRNAs that harbor binding domains for enzymes and their substrates are likely to function as scaffolds to connect two or more proteins (Figure E). To date, circ‐Foxo3 is the best example of displaying a variety of tertiary structures in various cell/tissue environments . In the mouse fibroblast NIH3T3 cell line, circ‐Foxo3 can bind to cyclin‐dependent kinase inhibitor 1 (p21) and cyclin‐dependent kinase 2 (CDK2), and this binding represses cell cycle entry .…”

Section: Functions Of Circrnasmentioning

confidence: 99%

Circular RNAs in hepatocellular carcinoma: Functions and implications

Jiang

et al. 2018

Cancer Medicine

107

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At present, as hotspot members of the noncoding RNA network, circular RNAs (circRNAs) with distinct properties and diverse pathophysiological functions are being increasingly delineated. CircRNAs play roles at the epigenetic, transcriptional and posttranscriptional regulatory levels. Major studies have focused on their functions as efficient microRNA sponges. The validated number of endogenous circRNAs involved in hepatocellular carcinoma (HCC) continues to increase. Altered circRNA expression is associated with HCC occurrence, invasion, and metastasis. Moreover, the aberrant expression of circRNAs is also significantly related to HCC tumor stage, size, differentiation and metastasis. Because they are exceptionally stable, highly conserved and have tissue‐specific expression patterns, some circRNAs, including hsa_circ_0004018, hsa_circ_0003570, and hsa_circ_0005075, may be potential markers for the diagnosis of HCC. We herein summarize the current knowledge of HCC‐associated circRNAs and present their implications for carcinogenesis and their potential value as diagnostic and prognostic biomarkers. Finally, we discuss the future directions of studies on HCC‐associated circRNAs.

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Section: Functions Of Circrnasmentioning

confidence: 99%

Circular RNAs in hepatocellular carcinoma: Functions and implications

Jiang

et al. 2018

Cancer Medicine

107

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“…Despite established investigations of miRNA and lncRNA interactions, lncRNA-RBP binding activity is not well explored in a context of post-transcriptional regulation. Other non-coding RNAs like circular RNAs have been reported to act as protein binding sponges [44] and lncRNAs have been reported to act as a binding sponge for the Hur protein [45]. However, this study identifies many RBPs binding to a handful of lncRNAs which act as a binding sponge.…”

Section: Discussionmentioning

confidence: 78%

Long non-coding RNA expression levels modulate cell-type specific splicing patterns by altering their interaction landscape with RNA-binding proteins

Porto

Daulatabad

Janga

2019

Preprint

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Background: Recent developments in our understanding of the interactions between long non-coding RNAs (lncRNAs) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases.Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks.Results: Analysis of alternative splicing events across 39 lncRNA knockdown and wildtype RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 11630 skipped exon events and 5895 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockdown were specific to the cell type, in tandem, the functions annotated to the genes affected by alternative splicing across each lncRNA knockdown also displayed cell type specificity. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions, to observe cell type specific alternative splice event RBP binding preference.Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs, and their downstream functions. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner. KeywordsLong non-coding RNA, cell type specific, alternative splicing, functional enrichment, RNAbinding proteins, protein binding lncRNA sponges, secondary RNA structure, and cancer.

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“…As pre-mRNA splicing is dictated by competitions between alternative pairing of 5′ and 3′ splice sites and backsplicing during circRNA generation affects the splicing pattern of the remaining pre-mRNA, cir-cRNAs modulate alternative splicing as a process regardless of the functionalities of circRNAs produced [52]. CircR-NAs can also sponge RBPs or RNP complexes to prevent them from acting, provide a protective reservoir of these factors, and deliver them to particular subcellular locations [58]. Lastly, the protein-coding function of circRNAs has been recently identified but still lack sufficient evidence, and novel approaches such as the 'intron-mediated enhancement system' have been proposed to investigate circRNA proteincoding functionalities through increasing circRNA formation [59].…”

Section: Regulationmentioning

confidence: 99%

RNA: interactions drive functionalities

2019

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RNA is produced from the majority of human genomic sequences, although only a relatively small portion of these transcripts has known functions. Diverse RNA species interact with RNA, DNA, proteins, lipids, and metabolites to form intricate molecular networks. In this review, we attempt to delineate diverse RNA functions by interaction types between RNA and other macromolecules. Through such interactions RNAs participate in essentially every major molecular function and process, including information flow and storage, environment sensing, signal transduction, and gene regulation at transcriptional and posttranscriptional levels. Through such interactions, RNAs promote or inhibit diverse biological processes, and act as catalyzer or quencher to modulate the pace of these progresses. Alterations and personal variations of these interactions are mechanistically coupled with disease etiology and phenotypical variations for clinical use.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Identifying and Characterizing circRNA-Protein Interaction

Cited by 476 publications

References 54 publications

Circular RNAs in hepatocellular carcinoma: Functions and implications

Circular RNAs in hepatocellular carcinoma: Functions and implications

Long non-coding RNA expression levels modulate cell-type specific splicing patterns by altering their interaction landscape with RNA-binding proteins

RNA: interactions drive functionalities

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