scholarly journals Circular RNA translation – new discovery and challenges

Author(s):  
Qingqing Miao ◽  
Bing Ni ◽  
Jun Tang

The circular (circ)RNAs are a newly recognized group of noncoding (nc)RNAs. Research to characterize the functional features of circRNAs has uncovered distinctive profiles of conservation, stability, specificity and complexity. However, a new line of evidence has indicated that although circRNAs can function as ncRNAs, such as in the role of miRNA sponges, they are also capable of coding proteins. To date, several circRNAs have been verified to be able to translate proteins or peptides with functions that mainly influence the functions of their maternal genes. These findings greatly broaden our research approach and the knowledge of ncRNAs, meanwhile these findings also raise questions about whether circRNA is still classified as non-coding RNA. Here, we systematically summarize the history and evidence for the translation of circRNAs, including the evolution implications, molecular structures, regulation and mechanism, experimental validation and computational prediction for the coding ability of circRNAs.

2019 ◽  
Author(s):  
Qingqing Miao ◽  
Bing Ni ◽  
Jun Tang

The circular (circ)RNAs are a newly recognized group of noncoding (nc)RNAs. Research to characterize the functional features of circRNAs has uncovered distinctive profiles of conservation, stability, specificity and complexity. However, a new line of evidence has indicated that although circRNAs can function as ncRNAs, such as in the role of miRNA sponges, they are also capable of coding proteins. To date, several circRNAs have been verified to be able to translate proteins or peptides with functions that mainly influence the functions of their maternal genes. These findings greatly broaden our research approach and the knowledge of ncRNAs, meanwhile these findings also raise questions about whether circRNA is still classified as non-coding RNA. Here, we systematically summarize the history and evidence for the translation of circRNAs, including the evolution implications, molecular structures, regulation and mechanism, experimental validation and computational prediction for the coding ability of circRNAs.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10718
Author(s):  
Qingqing Miao ◽  
Bing Ni ◽  
Jun Tang

The circular (circ)RNAs are a newly recognized group of noncoding (nc)RNAs. Research to characterize the functional features of circRNAs has uncovered distinctive profiles of conservation, stability, specificity and complexity. However, a new line of evidence has indicated that although circRNAs can function as ncRNAs, such as in the role of miRNA sponges, they are also capable of coding proteins. This discovery is no accident. In the last century, scientist detected the ability of translate in some virus and artificial circRNAs. Artificial circRNA translation products are usually nonfunctional, whereas natural circRNA translation products are completely different. Those new proteins have various functions, which greatly broadens the new ideas and research direction for our research. These series findings also raise questions about whether circRNA is still classified as non-coding RNA. Here, we summarize the evidence concerning translation potential of circRNAs, including synthetic and endogenous circRNA translation ability, and discuss the mechanisms of circRNA translation.


2018 ◽  
Author(s):  
Andrew Dhawan ◽  
Adrian L. Harris ◽  
Francesca M. Buffa ◽  
Jacob G. Scott

AbstractOscillations are crucial to the sustenance of living organisms, across a wide variety of biological processes. In eukaryotes, oscillatory dynamics are thought to arise from interactions at the protein and RNA levels; however, the role of non-coding RNA in regulating these dynamics remains understudied. In this work, using a mathematical model, we show how non-coding RNA acting as microRNA (miRNA) sponges in a conserved miRNA - transcription factor feedback motif, can give rise to oscillatory behaviour. Control of these non-coding RNA can dynamically create oscillations or stability, and we show how this behaviour predisposes to oscillations in the stochastic limit. These results, supported by emerging evidence for the role of miRNA sponges in development, point towards key roles of different species of miRNA sponges, such as circular RNA, potentially in the maintenance of yet unexplained oscillatory behaviour. These results help to provide a paradigm for understanding functional differences between the many redundant, but distinct RNA species thought to act as miRNA sponges in nature, such as long non-coding RNA, pseudogenes, competing mRNA, circular RNA, and 3’ UTRs.Author summaryWe analyze the effects of a newly discovered species of non-coding RNA, acting as microRNA (miRNA) sponges, on intracellular signalling dynamics. We show that oscillatory behaviour can arise in a time-varying manner in an over-represented transcriptional feedback network. These results point towards novel hypotheses for the roles of different species of miRNA sponges, such as their increasingly understood role in neural development.


2021 ◽  
Author(s):  
Chen Chang ◽  
Gang Ma ◽  
Edwin Cheung ◽  
Andrew P. Hutchins

AbstractRNA N6-Methyladenosine (m6A) is the most abundant mRNA modification, and forms part of an epitranscriptomic system that modulates RNA function. RNA modifications can be reversibly catalyzed by several specific enzymes, and those modifications can be recognized by RNA binding proteins that in turn regulate biological processes. Although there are many reports demonstrating m6A participation in critical biological functions, this exploration has mainly been conducted through the global knockout or knockdown of the writers, erasers, or readers of m6A. Consequently, there is a lack of information about the role of m6A on single transcripts in biological processes, posing a challenge in understanding the biological functions of m6A. Here, we demonstrate a CRISPR/dCas13a-based RNA m6A-editor which can target mRNAs using single crRNA or multiple crRNAs array to methylate or demethylate m6A. We systematically assay its capabilities to enable the targeted rewriting of m6A dynamics, including modulation of circular RNA translation and transcript half-life. Finally, we demonstrate the utility of the system by specifically modulating XIST m6A levels, which can control X chromosome silencing and activation. Based on our editors, m6A on single and multiple transcripts can be modified to allow the exploration of the role of m6A on in biological processes.


2020 ◽  
Vol 21 (2) ◽  
pp. 456 ◽  
Author(s):  
André F. Gabriel ◽  
Marina C. Costa ◽  
Francisco J. Enguita

Non-coding regulatory RNAs are generated as a core output of the eukaryotic genomes, being essential players in cell biology. At the organism level, they are key functional actors in those tissues and organs with limited proliferation capabilities such as the heart. The role of regulatory networks mediated by non-coding RNAs in the pathophysiology of cardiovascular conditions is starting to be unveiled. However, a deeper knowledge of the functional interactions among the diverse non-coding RNA families and their phenotypic consequences is required. This review presents the current knowledge about the functional crosstalk between circRNAs and other biomolecules in the framework of the cardiovascular diseases.


Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 258 ◽  
Author(s):  
Man Wang ◽  
Fei Yu ◽  
Peifeng Li

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. HCC patients are commonly diagnosed at an advanced stage, for which highly effective therapies are limited. Moreover, the five-year survival rate of HCC patients remains poor due to high frequency of tumor metastasis and recurrence. These challenges give rise to the emergent need to discover promising biomarkers for HCC diagnosis and identify novel targets for HCC therapy. Circular RNAs (circRNAs), a class of long-overlook non-coding RNA, have been revealed as multi-functional RNAs in recent years. Growing evidence indicates that circRNA expression alterations have a broad impact in biological characteristics of HCC. Most of these circRNAs regulate HCC progression by acting as miRNA sponges, suggesting that circRNAs may function as promising diagnostic biomarkers and ideal therapeutic targets for HCC. In this review, we summarize the current progress in studying the functional role of circRNAs in HCC pathogenesis and present their potential values as diagnostic biomarkers and therapeutic targets. In-depth investigations on the function and mechanism of circRNAs in HCC will enrich our knowledge of HCC pathogenesis and contribute to the development of effective diagnostic biomarkers and therapeutic targets for HCC.


2021 ◽  
Vol 27 (2) ◽  
pp. 3793-3798
Author(s):  
Yordanka Doneva ◽  
◽  
Veselin Valkov ◽  
Yavor Kashlov ◽  
Galya Mihaylova ◽  
...  

Circular RNA (circRNAs) belong to the long non-coding RNA family, but unlike the linear RNA in circular RNA, the 3’ and 5’ end in the RNA molecule are joined together, forming their circular structure. Until recently, circRNAs have been believed to be a side product of splicing, but now it is known that they have a wide range of biological functions, from regulators of gene expression to regulators of other non-coding RNAs - microRNAs (miRNAs). CircRNAs have the potential of being therapeutic targets and biomarkers for diseases. There are little data and only several investigations about this type of RNAs in myocardial infarction in humans. This review summarizes the role of some new circRNA – miRNA interactions in the development of Myocardial Infarction.


2021 ◽  
Vol 04 (06) ◽  
pp. 01-13
Author(s):  
Yongjun Li

Myocardial infarction (MI), one of the cardiovascular diseases (CVDs) with high incidence and mortality rate, seriously endangers human health. The poor ways of fully repairing and regenerating the infarcted myocardium may have an impact on people's life quality, therefore scientists have devoted continuously to exploring the way of myocardial repair after MI so as to strive for a better prognosis of these patients. In recent years, non-coding RNAs (ncRNAs) have been identified and become one of the exciting fields of research in the development of CVDs. In a wide range of areas, more and more research has found that ncRNAs play important roles in myocardial repair. This review mainly introduces some strategies for myocardial repair and the role or mechanism of microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA) and circRNA/lncRNA-miRNA-mRNA regulatory axis in the repair of myocardial tissue after MI, in order to build a better understanding and find new therapeutic targets for MI.


Diagnostics ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 60 ◽  
Author(s):  
Marvin Lim ◽  
Anne-Marie Baird ◽  
John Aird ◽  
John Greene ◽  
Dhruv Kapoor ◽  
...  

The treatment landscape of prostate cancer has evolved rapidly over the past five years. The explosion in treatment advances has been witnessed in parallel with significant progress in the field of molecular biomarkers. The advent of next-generation sequencing has enabled the molecular profiling of the genomic and transcriptomic architecture of prostate and other cancers. Coupled with this, is a renewed interest in the role of non-coding RNA (ncRNA) in prostate cancer biology. ncRNA consists of several different classes including small non-coding RNA (sncRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). These families are under active investigation, given their essential roles in cancer initiation, development and progression. This review focuses on the evidence for the role of RNAs in prostate cancer, and their use as diagnostic and prognostic markers, and targets for treatment in this disease.


2016 ◽  
Author(s):  
Franziska Metge ◽  
Lisa F Czaja-Hasse ◽  
Richard Reinhardt ◽  
Chistoph Dieterich

Circular RNAs (circRNAs) belong to a recently re-discovered species of RNA that emerge during RNA maturation through a process called back-splicing. A downstream 5’ splice site is linked to an upstream 3’ splice site to form a circular transcript instead of a canonical linear transcript. Recent advances in next-generation sequencing (NGS) have brought circRNAs back into the focus of many scientists. Since then, several studies reported that circRNAs are differentially expressed across tissue types and developmental stages, implying that they are actively regulated and not merely a by-product of splicing. Though functional studies have shown that some circRNAs could act as miRNA-sponges, the function of most circRNAs remains unknown. To expand our understanding of possible roles of circular RNAs, we propose a new pipeline that could fully characterizes candidate circRNA structure from RNAseq data – FUCHS: FUll CHaracterization of circular RNA using RNA- Sequencing. Currently, most computational prediction pipelines use back-spliced reads to identify circular RNAs. FUCHS extends this concept by considering all RNA-seq information from long reads (typically > 150 bp) to learn more about the exon coverage, the number of double break point fragments, the different circular isoforms arising from one host-gene, and the alternatively spliced exons within the same circRNA boundaries. This new knowledge will enable the user to carry out differential-motif enrichment and miRNA-seed analysis to determine potential regulators during circRNA biogenesis. FUCHS is an easy-to-use Python based pipeline that contributes a new aspect to the circRNA research. The pipeline is available as git repository: https://github.com/dieterich-lab/FUCHS


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