Emerging Role of Circular RNA–Protein Interactions

Das, Arundhoti; Sinha, Tanvi; Shyamal, S.; Panda, Amaresh C.

doi:10.3390/ncrna7030048

Cited by 59 publications

(49 citation statements)

References 100 publications

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“…They are rather more stable in comparison with their linear counterparts due to their resistance to ribonuclease (RNase) activities 25 . Circular RNAs have been proposed to function by means of miRNA sponging 26 , 27 , regulating transcription 28 , 29 and interacting with RNA-binding proteins (RBPs) 14 , 18 , 30 , 31 . Genome wide analysis has also demonstrated that circRNAs are evolutionary conserved among species 32 , 33 .…”

Section: Regulation Of Hippo-yap Signaling Axis By Circrnasmentioning

confidence: 99%

Circular RNAs modulate Hippo-YAP signaling: functional mechanisms in cancer

Qadir¹,

Li²,

Yang³

2022

Theranostics

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The Hippo signaling pathway is an evolutionarily conserved network that regulates organ size and tissue homeostasis in mammals. This pathway controls various cell functions, such as growth, proliferation, survival, apoptosis, and stemness by switching 'on' or 'off' its inhibitory and/or transcriptional module, thereby regulating target gene(s) expression. Altered Hippo signaling has been implicated in various forms of cancers. Increasing evidence suggests cross-talk between the Hippo signaling pathway and non-coding RNAs, in particular circular RNAs (circRNAs). In this context, the current review presents the mechanistic interplay between the Hippo pathway and related circRNAs in various forms of cancers, along with the capabilities of these circRNAs to function either as tumor suppressors or oncogenes through miRNA sponging or protein binding mechanisms. Furthermore, we discuss the constraints and limitations in circRNA mechanistic studies while highlighting some outstanding questions regarding the roles of circRNAs associated with the Hippo-YAP pathway in cancer. Finally, we delineate the potential of these circRNAs to be employed as diagnostic and prognostic biomarkers, as well as molecular hotspots for cancer therapy.

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Section: Regulation Of Hippo-yap Signaling Axis By Circrnasmentioning

confidence: 99%

Circular RNAs modulate Hippo-YAP signaling: functional mechanisms in cancer

Qadir¹,

Li²,

Yang³

2022

Theranostics

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“…Due to the closed circular nature, circRNAs are resistant to exonucleases and very stable compared to linear RNAs. circRNAs have been reported to regulate gene expression by acting as sponges for RNA-binding proteins (RBPs) and miRNAs ( Panda, 2018 ; Das et al, 2021 ). Also, a few circRNAs are translated into polypeptides with the cap-independent translation mechanisms, and some circRNAs regulate transcription by associating with snRNA and RNA pol II ( Bose and Ain, 2018 ; Sinha et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential circRNA-microRNA-mRNA Regulatory Network in Skeletal Muscle

Das

Shyamal

Sinha

et al. 2021

Front. Mol. Biosci.

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Circular RNAs (circRNAs) are a newly discovered family of regulatory RNAs generated through backsplicing. Genome-wide profiling of circRNAs found that circRNAs are ubiquitously expressed and regulate gene expression by acting as a sponge for RNA-binding proteins (RBPs) and microRNAs (miRNAs). To identify circRNAs expressed in mouse skeletal muscle, we performed high-throughput RNA-sequencing of circRNA-enriched gastrocnemius muscle RNA samples, which identified more than 1,200 circRNAs. In addition, we have identified more than 14,000 and 15,000 circRNAs in aging human skeletal muscle tissue and satellite cells, respectively. A subset of abundant circRNAs was analyzed by RT-PCR, Sanger sequencing, and RNase R digestion assays to validate their expression in mouse skeletal muscle tissues. Analysis of the circRNA-miRNA-mRNA regulatory network revealed that conserved circNfix might associate with miR-204-5p, a suppressor of myocyte enhancer factor 2c (Mef2c) expression. To support the hypothesis that circNfix might regulate myogenesis by controlling Mef2c expression, silencing circNfix moderately reduced Mef2c mRNA expression and inhibited C2C12 differentiation. We propose that circNfix promotes MEF2C expression during muscle cell differentiation in part by acting as a sponge for miR-204-5p.

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“…CircRNAs are lncRNAs that are generated through backsplicing of 1 or more exons that is facilitated by RNA binding proteins (RBPs). CircRNAs can localize to the nucleus and cytoplasm and can be secreted through exosomes [ 110 , 111 ]. They can regulate gene expression both at the transcriptional and post-transcriptional level.…”

Section: Glis Circular Rnasmentioning

confidence: 99%

GLIS1-3: Links to Primary Cilium, Reprogramming, Stem Cell Renewal, and Disease

Jetten

Scoville

Kang

2022

Cells

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The GLI-Similar 1-3 (GLIS1-3) genes, in addition to encoding GLIS1-3 Krüppel-like zinc finger transcription factors, also generate circular GLIS (circGLIS) RNAs. GLIS1-3 regulate gene transcription by binding to GLIS binding sites in target genes, whereas circGLIS RNAs largely act as miRNA sponges. GLIS1-3 play a critical role in the regulation of many biological processes and have been implicated in various pathologies. GLIS protein activities appear to be regulated by primary cilium-dependent and -independent signaling pathways that via post-translational modifications may cause changes in the subcellular localization, proteolytic processing, and protein interactions. These modifications can affect the transcriptional activity of GLIS proteins and, consequently, the biological functions they regulate as well as their roles in disease. Recent studies have implicated GLIS1-3 proteins and circGLIS RNAs in the regulation of stemness, self-renewal, epithelial-mesenchymal transition (EMT), cell reprogramming, lineage determination, and differentiation. These biological processes are interconnected and play a critical role in embryonic development, tissue homeostasis, and cell plasticity. Dysregulation of these processes are part of many pathologies. This review provides an update on our current knowledge of the roles GLIS proteins and circGLIS RNAs in the control of these biological processes in relation to their regulation of normal physiological functions and disease.

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Emerging Role of Circular RNA–Protein Interactions

Cited by 59 publications

References 100 publications

Circular RNAs modulate Hippo-YAP signaling: functional mechanisms in cancer

Circular RNAs modulate Hippo-YAP signaling: functional mechanisms in cancer

Identification of Potential circRNA-microRNA-mRNA Regulatory Network in Skeletal Muscle

GLIS1-3: Links to Primary Cilium, Reprogramming, Stem Cell Renewal, and Disease

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