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Biochimica et Biophysica Acta (BBA) - Gene regulation mechanisms
Volume 1862, Numbers 11–12,
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CircularARNare a recently discovered class of RNA that is formed by covalently joining the 5' and 3' ends of an RNA. Pre-mRNAs generate circular RNAs through a subsequent splicing mechanism. Whereas in linear splicing a 5' splice site is connected to a downstream 3' splice site, in reverse splicing the 5' splice site is connected to an upstream 3' splice site. Both mechanisms use thesplicedsomefor catalysis. For posterior splicing to occur, the posterior splicing sites often must be in close proximity, which is accomplished by the formation ofsecondary structuresin the pre-mRNA. In general, these pre-mRNA structures are formed by RNA base pairing between complementaryflanking stringsposterior splice sites. Proteins can abolish theseRNA structuresby binding to one of the complementary strands. However, proteins can also promote back-splicing without strong RNA structures throughmultimerizationafter binding to the intronic regions flanking the circular exons. inhumans,aluminum-elements comprising about 11% of theHuman genomeare the best characterized elements that generate structures that promote the formation of circular RNA. Therefore, the intronic structures of pre-mRNAs contribute to the formation of circular RNAs.
circular RNAs (circRNA) are covalently closed RNAs that are expressed in all branches of life . The majority of circRNAs are generated through subsequent splicing of pre-mRNA  where a 5' downstream splice site connects to an upstream 3' splice site (Fig. 1A). Most circRNAs contain exons of mRNA, but circRNAs composed of pre-mRNA introns have also been detected . Other mechanisms for creating circRNAs such as tRNA splicing , tetrahymena rRNA self-splicing , and the formation of circular viroid RNAs [6,7] also exist, but they are much less common.
In general, circRNAs are much lower in abundance than linear mRNAs and were considered by early reports to be splicing artifacts . As circRNAs lack a polyadenosine tail, they are reduced in libraries created by oligo dT priming. Its widespread expression only became apparent when next generation sequencing techniques were developed . It is currently estimated that overall, circRNAs comprise 0.8 to 1% of mRNAs [9,10].
The general function of circRNAs remains enigmatic. CircRNAs accumulate in the cytosol via an export pathway that depends on the RNA helicases UAP56 (DDX39B) and URH49 (DDX39A) , pointing to functions in the cytosol. Some circRNAs have been shown to sequester miRNA, acting as "sponges" [12,13], indirectly influencing mRNA abundance. Numerous circRNAs are associated with ribosomes  and proof-of-principle experiments indicated that they can be translated [, , , , , ]. In drosophila and humans, the highest diversity and expression of circRNAs has been found in the brain and increases with aging [, , ] suggesting tissue-specific roles for circRNAs.
The vast majority of exons in circRNAs are also present in their linear counterparts, suggesting competition between linear and reverse splicing. In some cases, this competition can reduce linear mRNA expression [2,24,25], indicating a role for some circRNA in mRNA expression.
circular RNA types
The highest expressed individual circRNAs are generated by a single large exon through a back splicing mechanism . In general, most circRNAs contain multiple exons, mostly two exons. The number of circRNA transcripts decreases with the number of its forming exons . Like linear mRNAs, circRNAs can be alternatively spliced [26,27]. Many circRNAs contain intronic sequences, but most circRNAs lack intronic sequences, suggesting that multi-exon circRNAs are generated later.
Post-splicing that creates circRNA uses the same splicing machinery and most of the splicing enhancers and silencers as linear pre-mRNA splicing. Therefore, the exons present in circRNAs are surrounded by canonical splice sites in the pre-mRNA and circRNA formation is sensitive to splicing inhibition . SiRNA-mediated depletion of splicing factors increased the formation of some circRNAs while the corresponding mRNAs were reduced, suggesting a coupling between circRNA and mRNA formation .
Recognition of subsequent splice sites depends on the secondary structure of the pre-mRNA
For back-splicing to occur, the splicing sites involved must be in close contact, either through secondary structure in the RNA (Fig. 1A) or through protein interactions (Fig. 1B). In most cases studied, these structures are generated through base pairing of complementary RNA sequences within the same pre-mRNA molecule. Protein interactions for tremor I (QKI) have been shown to bind to short intronic recognition sites flanking downstream splicing sites resulting in circRNA
aluminumelements form secondary structures that promote the formation of human circular RNA
Sequencing of human circRNAs revealed that they are often flanked byaluminumelements at their genomic location [2,26].aluminumThe elements are approximately 300 nucleotides (nt) long and short interspersed nuclear elements (SINEs) [, , ] that were derived from 7SL-RNA in the primitive primate lineage [51,52 ] (Fig. 2A,B). There are more than a millionaluminumcopies of elements in the human genome that comprise about 11% of the human genome .aluminumElements continue to be amplified via a derivative of polymerase III.
Correlations between double-stranded pre-mRNA structures and circRNA formation have been tested experimentally. Current reporter gene constructs and experimentally validated double-stranded RNA structures are summarized in Fig. 3. Double-stranded structures can be surprisingly small. For example, the experimentally determined structure necessary to form circRNAs that are formed from exon 2/3 of ZKSCAN1 is only 36 nt long and contains 7 mismatches, although the natural repeat is much longer , (Fig.
Despite their low expression compared to their linear counterparts, circRNAs could prove to be biologically very important. An increasing number of studies now show that circRNAs can form proteins [16,62]. CircRNAs are highly expressed in the brain, where they might encode novel peptide hormones that are small, reflecting the short reading frames of circRNAs, and function at low concentrations. For example, α-melanocyte-stimulating hormone (α-MSH), generated from POMC, is a peptide
expressions of gratitude
This work was supported by theDefense Department AZ180075and aJacqueline Noonan's Endowment(H.H). JRW received the Graduate Research Excellence Award from the University of Kentucky School of Medicine.
- yzhanget al.
RNA in circular intronic wide coding(Video) What Is Circular RNA | circRNA | Types Of Circular RNA |
minor The cell
- XFliet al.
A circularized transcript of exon 2 of the sodium-calcium exchanger
J. Biol. chemistry
- A.Costelloet al.
Continuous translation of circularized mRNA improves recombinant protein titer
- J. O.Westholmet al.
Whole-genome analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation
- A.Rybak-Loboet al.
Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed.
minor The cell
- X. O.zhanget al.
Exon circularization mediated by complementary sequenceSee AlsoA Unique Circular RNA Expression Pattern in the Peripheral Blood of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome PatientsThe design and synthesis of circular RNAs.Study links Barrett's esophagus cDNA to cancerCircRNA-mediated ceRNA regulatory network during flower development and color formation in Melastoma candidum
- qChuet al.
PlantcircBase: a database for plant circular RNAs
- S.starkeet al.
Exon circularization requires canonical splicing signals
- JRweldinget al.
Human MAPT locus generates circular RNAs
biochemistry Biography. Act Mol. Basis Dis.
- SJTo connectet al.
RNA-binding protein tremor regulates circRNA formation
CircRNA biogenesis competes with pre-mRNA splicing
minor The cell
Circular transcripts of the testis-determining Sry gene in adult mouse testes
Inverted repeats are required for circularization of mouse testis Sry transcript
Intron sequence analysis reveals distinctive features of circular RNA biogenesis in animals
ALU alternative regulation for gene expression
Cell Biol Trends.
RNA editing, DNA recoding, and the evolution of human cognition
Circular RNA is expressed through the eukaryotic tree of life.
Circular RNAs are abundant, conserved, and associated with ALU repeats
Metazoan tRNA introns generate stable circular RNAs in vivo
The autocatalytic cyclization of an excised RNA intervening sequence is a cleavage-ligation reaction.
Viroids are single-stranded covalently closed circular RNA molecules that exist as highly paired rod-like structures.
proc. National Academy of Science USA
Circular DNA tumor viruses produce circular RNAs
proc. National Academy of Science USA
Mis-splicing produces circular RNA molecules
Circular RNAs are the predominant transcription isoform of hundreds of human genes in various cell types.
Detection and characterization of circular RNAs
An evolutionarily conserved length-dependent pathway controls the nuclear export of circular RNAs
Natural RNA circles function as efficient microRNA sponges
Circular RNAs act as miRNA sponges
Adv. Exp. Medicina. Biol.
Information on the biogenesis and potential functions of exonic circular RNA
Rolling circle translation of circular RNA in living human cells
Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis
minor The cell
A novel protein encoded by a circular circPPP1R12A RNA promotes tumor pathogenesis and colon cancer metastasis through Hippo-YAP signaling
A peptide encoded by the circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma
Spatiotemporal regulation of circular RNA expression during porcine embryonic brain development
From the comparative study of a circRNA originating from a mammalian ATXN2L intron to understanding the genesis of circRNAs derived from lariat introns
2022, Biochimica et Biophysica Acta - Gene regulation mechanisms
We know that ciRNAs are much rarer than exonic circRNAs, for which ortholog conservation studies have been more numerous [34,58–61]. The ability to produce exonic circRNA appears to be primarily related to the genomic structure of genes (reviewed topic [62,63] in 2019, [12,60,64,65]), which is often conserved. We show that the "conservation" of ciRNA-ATXN2L in mammals is related to intronic sequence features.
Circular intronic RNAs (ciRNAs) have not yet been explored in terms of the mechanisms for their appearance. we consider theATXN2LIntron lariat-derived circular RNA (ciRNA-ATXN2L) as an opportunity to perform a cross-species examination of ciRNA genesis. To this end, we investigated 207 data sets from 4 tissues and from 13 mammalian species. While in eight species ciRNA-ATXN2L was never detected, in pigs and rabbits ciRNA-ATXN2L was expressed in all tissues and sometimes at very high levels. Bovine tissues were an intermediate case and only trace amounts of ciRNA-ATXN2L were detected in macaques and cats. The pattern of ciRNA-ATXN2L restricted to only five species is not related to a particular evolution of intronic sequences. To power our analysis, we considered an additional 221 introns, including 80 introns where a lariat-derived ciRNA was previously described. The main driver of micro-ciRNA genesis (<155 nt like ciRNA-ATXN2L) appears to be the absence of a canonical "A" (i.e., a "tnA" located in the usual branching region) to construct the loop around this adenosine. The balance between available "non-canonical-A" (no ciRNA genesis) and "non-A" (ciRNA genesis) to use as a point of branching to construct the lariat could modify the expression level of ciRNA-ATXN2L.In addition, the rare location of the 2′-5′ linkage in an open RNA secondary structure could also negatively affect the lifespan of ciRNAs (macaco ciRNA- ATXN2L) Our analyzes suggest that ciRNA-ATXN2L is likely a non-functional splicing remnant This study provides a better understanding of the origin of ciRNAs, especially the drivers of micro ciRNA genesis.
Emerging functions of circular RNAs in systemic lupus erythematosus
2021, Molecular Therapy - Nucleic Acids
Based on the biogenesis of different genomic regions, circRNAs can be classified into three main types: exonic circRNAs (EcRNAs), which contain one or more exons derived from alternative splicing and account for more than 80% of all known circRNAs;13 intronic circRNAs ( ciRNA), which only contain introns and may depend on a consensus motif containing a specific base distribution;14 and exon-intron circRNAs (EIcRNA), which are made up of both exon and intron elements (Figure 1). 15 Since circRNAs are mainly generated by reverse splicing of pre-mRNAs, their expression is also determined by the levels of transcription of pre-mRNAs, which depend on transcription factor activity and epigenetic modifications, such as methylation, acetylation, and ncRNAs.16–19 circRNA expression is also modulated by the regulation of circularization, which involves three main hypothesized models: lariat-driven circularization, in which the formation of a lariat structure approaches the upstream splice acceptor and downstream donor prior to splicing; intron pairing-driven circularization, in which inverted complementary repeat sequences are combined into RNA duplexes and undergo alternative splicing; and RNA-binding protein (RBP)-mediated circularization, in which RBPs bind to flanking upstream and downstream introns to facilitate subsequent splicing of pre-mRNA circularization (Figure 1).13,20 –22(Video) Circular RNA | Structure | Function | Types | Importance
Circular RNAs (circRNAs) are a class of noncoding RNAs with covalently closed single-stranded structures that lack 5′–3′ polarity and a polyadenine tail. In recent years, a growing body of studies have been conducted to explore the roles of circRNAs in human disease. Systemic lupus erythematosus (SLE) is a severe autoimmune disorder characterized by the presence of autoantibodies and excessive inflammation, affecting multiple organs. Recent advances have begun to shed light on the functions of circRNAs in SLE, providing new insights into the pathogenesis of SLE and the latent ability to be translated into clinical applications. Here we briefly introduce these "star molecules" and summarize their functions in the LES. In addition, we describe the limitations of current studies and outline perspectives for future research.
Curcumin suppresses non-small cell lung cancer malignancy by modulating the circ-PRKCA/miR-384/ITGB1 pathway
2021, Biomedicine and Pharmacotherapy
There are four types of circRNAs, including intergenic circRNAs, intron circRNAs, exon circRNAs, and exon-intron circRNAs . Exon circRNAs, which are produced by pre-mRNA by back-splicing, account for more than 80% of all circRNA types . According to the ceRNA hypothesis, circRNAs can bind to microRNAs (miRs) via miR response elements, thereby sequestering miRs and regulating miR downstream targets .
Curcumin exerts a suppressive effect on tumor growth by acting as a modulator of multiple molecular targets. The hsa_circ_0007580 (circ-PRKCA) circular RNA accelerates the tumorigenesis of non-small cell lung cancer (NSCLC). However, it is not clear whether curcumin can regulate circ-PRKCA to inhibit NSCLC progression.
Cell viability, colony formation, apoptosis, migration and invasion were analyzed by cell counting kit 8 (CCK-8), clone plated, flow cytometry or Transwell assay. Expression of circ-PRKCA, microRNA (miR)-384, and ITGB1 (integrin beta 1 subunit) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Curcumin repressed NSCLC growth through regulation of circ-PRKCA expression and was validated using a xenograft assay. The targeting relationship between circ-PRKCA or ITGB1 and miR-384 was verified by a dual luciferase reporter assay. ITGB1 protein level was measured by Western blotting.
Circ-PRKCA and ITGB1 expression was elevated in NSCLC cells and tissues, but miR-384 had an opposite trend. After curcumin treatment, the expression trend of circ-PRKCA, miR-384 and ITGB1 in NSCLC cells was abrogated. Furthermore, curcumin prevented viability, colony formation, migration, invasion, and accelerated apoptosis of NSCLC cells, but these impacts were partially reversed by elevation of circ-PRKCA, downregulation of miR- 384 or overexpression of ITGB1. Furthermore, the inhibitory effect of curcumin on the xenograft tumor was further enhanced after circ-PRKCA knockdown. In particular, circ-PRKCA regulated ITGB1 expression through the miR-384 sponge in curcumin-treated NSCLC cells.
Curcumin inhibited NSCLC growth through downregulation of circ-PRKCA, which regulated ITGB1 expression via miR-384 adsorption. This study provided a new mechanism to understand how curcumin inhibited NSCLC progression.
Characteristics of circular RNAs generated by human survival motor neuron genes
2020, Cell Signaling
In several cases, an RNA:RNA duplex formed between complementary sequences upstream and downstream of 3 and 5, respectively, facilitates reverse splicing. In humans, such an RNA:RNA duplex is often formed by inverted Alu repeats [9,22,58]. Non-repeat sequences capable of forming an RNA:RNA duplex through long-distance interactions may also facilitate backsplicing, although such duplexes are difficult to predict due to the presence of alternative structures in long transcripts [59,60].
Circular RNAs (circRNAs) belong to a diverse class of stable RNAs that are expressed in all cell types. Its proposed functions include microRNA (miRNA) swelling, protein sequestration and trafficking, assembly of multimeric complexes, peptide production, and regulation of transcription. Backsplicing due to RNA structures formed by an exceptionally high number of Alu repeats leads to the production of a vast repertoire of circRNAs by humans.survival motor neurongenes,SMN1ySMN2, which codes for SMN, an essential multifunctional protein. Low levels of SMN due to deletion or mutation ofSMN1result in spinal muscular atrophy (SMA), a major genetic disease of infants and children. Mild SMA is also recorded in the adult population, broadening the spectrum of the disease. Here we reviewSMNcircRNAs with respect to their biogenesis, sequence characteristics, and potential functions. We also discuss howSMNCircRNAs could be exploited for diagnostic and therapeutic purposes.
A study of the transcripts generated by spinal muscular atrophy genes
2020, Biochimica et Biophysica Acta - Gene regulation mechanisms
SMN genes generate a vast repertoire of circRNA: >50 SMN circRNA species have so far been identified (Fig. 4) [72,73,76]. The generation of SMN circRNAs is generally attributed to backsplicing facilitated by RNA structures formed between inverted Alu repeats present within the transcribed region [72,93–95]. Depending on their exon content, SMN circRNAs are broadly classified into four types (Fig. 4) .
Humansurvival motor neuron(SMN) genes code for SMN, an essential multifunctional protein. Complete loss of SMN is lethal from the embryo, while low levels of SMN lead to spinal muscular atrophy (SMA), a major genetic disease of children and infants. Reduced SMN levels are associated with abnormal development of the heart, lungs, muscles, gastrointestinal system, and testicles. HeSMNThe loci have been shown to generate a wide repertoire of transcripts, including linear, backspliced, and trans RNAs, as well as antisense long noncoding RNAs. However, the functions of most of these transcripts remain unknown. Here we review the nature of the RNAs generated from theSMNloci and discuss their potential roles in cellular metabolism.
Small noncoding RNA within the endogenous spliceosome and regulation of alternative splicing
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1862, Numbers 11 and 12, 2019, Article 194406(Video) How to study Circular RNA expression and modifications?
Splicing and alternative splicing (AS), which occur in the endogenous spliceosome, play an important role in the regulation of gene expression, and defects in them are implicated in numerous human diseases, including cancer. Although the mechanism of the splicing reaction is well understood, the regulation of AS remains to be elucidated. One group of essential regulatory factors in gene expression are small non-coding RNAs (sncRNA): e.g. microRNA, primarily known for its inhibitory role in translation in the cytoplasm; and small nucleolar RNA, known for its role in non-coding RNA methylation in the nucleolus. Here I highlight a new aspect of sncRNAs found within the endogenous spliceosome. Assembled in non-canonical complexes and through different base pairing than their canonical ones, spliceosomal sncRNAs can potentially target different RNAs. Examples of spliceosomal snRNAs that regulate AS, regulate gene expression, and act in a quality control of AS are reviewed, suggesting novel roles for spliceosomal sncRNA.
This article is part of a special issue entitled: RNA Structure and Regulation of Splicing edited by Francisco Baralle, Ravindra Singh, and Stefan Stamm.
Circular RNA (circRNA) was an important bridge in the shift from the world of RNA to the world of DNA.
Journal of Theoretical Biology, Volumen 447, 2018, págs. 32-40
The concept that life on Earth began as an RNA world has been based on extensive experimentation showing that many of the building blocks necessary for living cells could be synthesized in the laboratory under conditions that approximate those of our world. primordial. Many of the building blocks of life have also been found in meteorites, indicating that meteorites may have been a source of these molecules or, more likely, that they represent the chemical library present in most or all bodies in the universe. after the big bang. Perhaps the most important support for the concept comes from the fact that some RNA species possess catalytic activity, ribozymes, and that RNA could be reverse transcribed into DNA. The thrust of numerous articles on this topic has been to explore how the molecules available on Earth, at its birth, gave rise to life as we know it today. This document focuses more on a reverse view of the subject. It does not address "how" the molecular building blocks were synthesized or how the "first" RNA molecules were synthesized. Clearly we can speculate about the variable environmental conditions and chemistry available on Earth billions of years ago. However, we will never be able to truly replicate the changing conditions or know the chemical composition of the Earth at the beginning of time. However, we can confirm that over millions, perhaps billions of years, the building blocks for life accumulated enough to initiate evolution towards an RNA world followed by our RNA/DNA world. Here we are trying to take information from our current knowledge of biology and by inference and backward extrapolation work to hypothesize biological events on the forward march from RNA to DNA. It is proposed that the primordial replicating RNA cell, the ribocyte, evolved from liposomes encompassing the reagents and products necessary for "life" and that ribonucleopeptide complexes formed membrane pores to support bidirectional transport of ions and molecules. to maintain biological functions and osmolarity. Circular RNA, circRNA, is proposed as a critical stable RNA molecule that served as the genetic precursor for the switch to DNA, and circRNA replication via a rolling-circle mechanism gave rise to the RNA complexity necessary for the genetic functions of circRNA. cell. The replicating ribocyte would have required protein synthesis as well as RNA replication, and a model for the synthesis of primordial encoded and non-encoded proteins is proposed. Finally, the change from the RNA to DNA world would have involved the synthesis of an RNA:DNA hybrid before the formation of dsDNA. If the hybrid were a circular molecule that eventually gave rise to a circular dsDNA molecule, he could predict that the primordial DNA cell would develop into a bacterial cell with a single circular chromosome. One would hope that continued speculation about the origin of life will stimulate new directions of research that may never fully answer the questions of the past, but will increase our ability to regulate potentially harmful biological events in the present and in the future.
RNA-binding protein tremor regulates circRNA formation
Cell, Volume 160, Number 6, 2015, pp. 1125-1134
Circular RNAs (circRNAs), formed by non-sequential reverse splicing of pre-mRNA transcripts, are a widespread form of noncoding RNA in animal cells. However, it is not clear whether most circRNAs represent splicing byproducts without function or are produced in a regulated manner to carry out specific cellular functions. We show that hundreds of circRNAs are regulated during the human epithelial-mesenchymal transition (EMT) and find that the production of more than one-third of the abundant circRNAs is dynamically regulated by the alternative splicing factor, Quaking (QKI), which in turn is regulated during EMT. . Furthermore, by modulating QKI levels, we show that the effect on circRNA abundance is dependent on intronic QKI-binding motifs. Critically, the addition of QKI motifs is sufficient to induce de novo circRNA formation from transcripts that are normally linearly spliced. These findings demonstrate that circRNAs are deliberately synthesized and regulated by cell-type-specific mechanisms, suggesting that they play specific biological roles in EMT.
Molecular choreography of pre-mRNA splicing by the spliceosome
Current Opinion in Structural Biology, Volume 59, 2019, pp. 124-133
The splicesome performs splicing of eukaryotic precursor messenger RNA (pre-mRNA) to remove non-coding introns through two sequential transesterification reactions, branching and exon ligation. The fidelity of this process is based on the recognition of conserved sequences in the intron and the dynamic compositional and structural rearrangement of this multi-megadalton machinery. Since atomic visualization of the active splice site in an endogenousSchizosaccharomyces pombespliceosome In 2015, high-resolution cryo-electron microscopy (cryo-EM) structures of other spliceosome intermediates began to uncover the molecular mechanism. Recent advances in the structural biology of the spliceosome clarify the mechanisms of its assembly, activation, disassembly, and exon ligation. Together, these discrete structural images give rise to a molecular choreography of the spliceosome.
Circular exonic RNAs: when RNA structure meets topology
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1862, Numbers 11 and 12, 2019, Article 194384
Although RNA circularization was first documented in the 1990s, the extent to which it occurred was not known until recent advances in high-throughput sequencing allowed widespread identification of circular RNAs (circRNAs). Despite this, many aspects of circRNA biogenesis, structure, and function still remain obscure. This review focuses on circular exonic RNAs, a subclass of circRNAs that are generated by backsplicing. Here, I hypothesize that RNA secondary structure may be the common factor promoting both exon skipping and splicosomal RNA circularization, and that subsequent splicing of double-stranded regions could generate topologically linked circRNA molecules. CircRNAs are manifested by the presence of tail-to-head exon junctions, which were previously attributed to post-transcriptional exon repeat and swapping. I review these observations and argue that reverse splicing does not automatically imply RNA circularization because tail-to-head exon junctions provide only local information about transcription architecture and are therefore insufficient in principle to determine circular topology. global. This article is part of a special issue entitled: RNA Structure and Regulation of Splicing edited by Francisco Baralle, Ravindra Singh, and Stefan Stamm.
Circular RNA expression: its possible regulation and function
Trends in Genetics, Volume 32, Number 5, 2016, pp. 309-316
In 2012, a new feature of eukaryotic gene expression emerged: the ubiquitous circular RNA (circRNA) expression of genes traditionally thought to express only linear noncoding (nc) or messenger RNA. CircRNAs are covalently closed circular RNA molecules that typically comprise exonic sequences and are spliced at canonical splice sites. This feature of gene expression was first recognized in humans and mice, but it was quickly learned that it was common in virtually all eukaryotes studied by molecular biologists. The abundance of circRNA, and even which alternatively spliced circRNA isoforms are expressed, varies by cell type and may exceed the abundance of the traditional linear ncRNA or mRNA transcript. CircRNAs are enriched in the brain and increase in abundance during fetal development. Together, these features raise fundamental questions regarding the regulation of circRNA incisand intrans, and its function.
© 2019 Elsevier B.V. All rights reserved.
Circular RNA (circRNA) is a novel endogenous non-coding RNA (ncRNA) that, like microRNA (miRNA), is a rapidly emerging RNA research topic. CircRNA, unlike traditional linear RNAs (which have 5' and 3' ends), has a closed-loop structure that is unaffected by RNA exonucleases.How are circular RNAs formed? ›
Circular RNAs can be produced by the direct ligation of 5′ and 3′ ends of linear RNAs, as intermediates in RNA processing reactions, or by “backsplicing,” wherein a downstream 5′ splice site (splice donor) is joined to an upstream 3′ splice site (splice acceptor).Which RNA viruses are circular? ›
Circular RNAs (circRNAs) are a recently identified class of ubiquitously expressed RNAs found in eukaryotes, archaea, and viruses. DNA viruses Kaposi's sarcoma-associated herpesvirus, Epstein–Barr virus, and human papillomavirus encode circRNAs.What is pre-mRNA made of? ›
Pre-mRNA is synthesized from a DNA template in the cell nucleus by transcription. Pre-mRNA comprises the bulk of heterogeneous nuclear RNA (hnRNA). Once pre-mRNA has been completely processed, it is termed "mature messenger RNA", or simply "messenger RNA".How many types of circular RNA are there? ›
There are three major types of circRNA: ecircRNA, ciRNA, and EIciRNA. EcircRNAs function mainly in the cytoplasm through the “microRNA sponge” mechanism, whereas EIciRNA and ciRNA accumulate in the nucleus and facilitate transcription of their parent genes via cis-regulatory effects.What is the structure of RNA called? ›
The RNA tertiary structure is the result of RNA folding, which creates a three-dimensional shape consisting of helices and grooves. RNA differs from DNA in that it contains a uracil nucleotide instead of thymine and carries a 2' hydroxyl group rather than a 2' hydrogen.Where are RNA formed? ›
Ribosomal RNA (rRNA) is the most common form of RNA found in cells – it makes up around 50% of the structure of the ribosomes. It is produced in the nucleus, before moving out into the cytoplasm to bind with proteins and form a ribosome. Transfer RNA (tRNA) is found in the cytoplasm and has a complex shape.What are the properties of circular RNA? ›
circRNAs are usually available in a wide range of cells and have shown tissue-specific expression as well as developmental specific expression. circRNAs are characterized by structural stability, conservation, and high abundance in the cell.What are circular RNAs in gene expression? ›
Circular RNAs (circRNAs) are stable and prevalent RNAs in eukaryotic cells that arise from back-splicing. Synthetic circRNAs and some endogenous circRNAs can encode proteins, raising the promise of circRNA as a platform for gene expression.Do humans have circular RNA? ›
Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types.
Circular RNAs are abundant, conserved, and associated with ALU repeats. Some viral genomes can also be in circular form, such as viroid plants and hepatitis D virus.Is viral RNA circular or linear? ›
Viral Circular RNAs and Their Possible Roles in Virus-Host Interaction. Circular RNAs (circRNAs) as novel regulatory molecules have been recognized in diverse species, including viruses. The virus-derived circRNAs play various roles in the host biological process and the life cycle of the viruses.Why is it called pre-mRNA? ›
The key difference between pre-mRNA and mRNA is that pre-mRNA is the first product of the transcribed gene and contains both non-coding sequences (introns) and coding sequences (exons) while mRNA is the second product of a transcribed gene which contains only coding sequences. Gene is the functional unit of heredity.What does pre-mRNA stand for? ›
Pre-mRNA splicing is one of the fundamental processes in the intrinsic and regulated gene expression in eukaryotes. It is a highly precise process that involves the removal of noncoding intronic sequences from the pre-mature RNA transcript (pre-mRNA) to produce the mature form of protein-coding messenger RNA (mRNA).What is the pre-mRNA translation? ›
During transcription, the enzyme RNA polymerase (green) uses DNA as a template to produce a pre-mRNA transcript (pink). The pre-mRNA is processed to form a mature mRNA molecule that can be translated to build the protein molecule (polypeptide) encoded by the original gene.What is the purpose of CircRNA? ›
CircRNA plays a regulating role in gene expression, and an essential role in the process of biological development, such as miRNA sponges, endogenous RNAs and biomarkers, as well as critical role in the diagnosis of diseases.What is the smallest circular RNA? ›
The smallest circRNA was found to be of 32 nt between positions 5,187-5,219 in the genome.What are the 4 structures of RNA? ›
RNA consists of four nitrogenous bases: adenine, cytosine, uracil, and guanine. Uracil is a pyrimidine that is structurally similar to the thymine, another pyrimidine that is found in DNA.What are the 3 types of RNA? ›
Three main types of RNA present in cells include messenger RNA (mRNA), ribosomal RNA (rRNA) and transfer RNA (tRNA). Messenger RNA (mRNA) is a single-stranded RNA molecule responsible for carrying genetic information from the nucleus to the cytoplasm for protein synthesis by ribosomes.What are the 4 types of RNA? ›
The four types of RNA are mRNA, tRNA, rRNA and heterogeneous nuclear RNA or hn RNA. they have different functional roles in the cell.
All of the RNA in a cell is made by DNA transcription, a process that has certain similarities to the process of DNA replication discussed in Chapter 5. Transcription begins with the opening and unwinding of a small portion of the DNA double helix to expose the bases on each DNA strand.What is mRNA called? ›
Messenger RNA (abbreviated mRNA) is a type of single-stranded RNA involved in protein synthesis. mRNA is made from a DNA template during the process of transcription.Where are the 3 types of RNA made? ›
mRNA is produced in the nucleus, as are all RNAs. The other two forms of RNA, ribosomal RNA (rRNA) and transfer RNA (tRNA), are involved in the process of ordering the amino acids to make the protein.Why is circular RNA stable? ›
The intracellular stability of circRNAs is due to their unique circular structure, which renders them resistant to exonucleases such as RNase R 27.Why is circular RNA more stable? ›
(1) Since, unlike linear RNA, circRNA is a covalently closed loop with no 5′end cap or 3′poly (A) tail structure, it is not easily degraded by exonuclease and is more stable than linear RNA (Suzuki and Tsukahara, 2014).How is circular RNA translated? ›
CircRNAs can be translated in cap-independent mechanism, including IRES (internal ribosome entry site)-initiated pattern, MIRES (m6A internal ribosome entry site) -initiated patterns, and rolling translation mechanism (RCA). CircRNA-encoded proteins harbour diverse functions similar to or different from host proteins.What is a circular DNA structure? ›
Circular DNA is a form of closed-loop DNA that has no ends. This type of DNA is found in the cytoplasm of most prokaryotic cells. Also, it is seen in organelles like chloroplasts and mitochondria. The plasmid DNA is a classic example of extrachromosomal circular DNA.Where is circular DNA found in humans? ›
The mitochondrial genome comprises a circular, histone-free DNA, present in one or more copies in every mitochondrion (2).Do eukaryotes have circular RNA? ›
Circular RNAs (circRNAs) are now recognized as large species of transcripts in eukaryotic cells.Who has circular DNA? ›
HPV has a circular DNA genome in which the viral late and early genes are separated by the transcriptional control region called URR or LCR. Functionally, the 850 bp HPV 16 URR can be divided into three parts: 1.
INTRODUCTION. Viruses have genomes composed of one or more molecules of RNA or DNA in linear or circular form.Which viruses are circular? ›
Most ssDNA viruses contain circular genomes that are replicated via rolling circle replication (RCR). ssDNA RCR is initiated by an endonuclease that bonds to and cleaves the positive strand, allowing a DNA polymerase to use the negative strand as a template for replication.Are all viruses circular? ›
Most viruses have icosahedral or helical capsid structure, although a few have complex virion architecture. An icosahedron is a geometric shape with 20 sides, each composed of an equilateral triangle, and icosahedral viruses increase the number of structural units in each face to expand capsid size.How does pre-mRNA become RNA? ›
In eukaryotes, mRNA precursors (pre-mRNAs) are transcribed by RNA polymerase II (Pol II) from the genome and must undergo extensive cotranscriptional processing to become mature mRNAs. The typical progression of pre-mRNA maturation involves 5′-end capping, splicing, and 3′-end cleavage and polyadenylation.How does pre-mRNA work? ›
Pre-mRNA splicing is a common post-transcriptional process used by eukaryotic organisms to generate multiple transcript isoforms from a single gene. This process expands substantially the variety of encoded proteins, thus providing another means of functional regulation .Why is pre-mRNA important? ›
Pre-mRNA splicing is a crucial process that allows proper progression of the cell cycle. Thus, inhibiting the spliceosome or silencing a specific splicing factor often promotes cell-cycle arrest.Where is pre-mRNA used? ›
Pre-mRNA splicing is essential for gene expression in mammalian cells in which most protein-coding genes are disrupted by intervening sequences (introns). The process to remove introns is efficient and precise, thus constituting the vast majority of constitutive splicing events in the cell.What is pre-mRNA modified by? ›
Eukaryotic pre-mRNAs are modified with a 5' methylguanosine cap and a poly-A tail. These structures protect the mature mRNA from degradation and help export it from the nucleus. Pre-mRNAs also undergo splicing, in which introns are removed and exons are reconnected with single-nucleotide accuracy.Why is pre-mRNA modified? ›
The pre-mRNA has to go through some modifications to become a mature mRNA molecule that can leave the nucleus and be translated. These include splicing, capping, and addition of a poly-A tail, all of which can potentially be regulated – sped up, slowed down, or altered to result in a different product.What are the three steps of pre-mRNA? ›
Three major events constitute pre-mRNA processing: (a) 5′-end capping, (b) splicing, and (c) 3′-end polyadenylation.
Translation takes place on ribosomes in the cell cytoplasm, where mRNA is read and translated into the string of amino acid chains that make up the synthesized protein.What is the difference between RNA and circular RNA? ›
Circular RNA (or circRNA) is a type of single-stranded RNA which, unlike linear RNA, forms a covalently closed continuous loop. In circular RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together.Is circular RNA double stranded? ›
CircRNA forms a double-stranded RNA stem-loop structure that binds to the double-stranded RNA-dependent protein kinase (PKR). In normal cells, the antiviral PKR molecule is bound to the stem-loop structure of circRNA, avoiding the immune response caused by overactivation.What is the main function of circular RNAs? ›
CircRNA plays a regulating role in gene expression, and an essential role in the process of biological development, such as miRNA sponges, endogenous RNAs and biomarkers, as well as critical role in the diagnosis of diseases.What does the RNA circle mean? ›
Circular RNA represents a functional molecule with roles in the regulation of transcription and splicing, microRNA sponge, and the modulation of protein–protein interaction. CircRNAs are involved in essential processes of life such as apoptosis, cell cycle, and proliferation.What are the 3 types of RNA What is the function of each type? ›
mRNA (messenger RNA): it provides the template for protein synthesis during translation. tRNA (transfer RNA): it brings amino acids and reads the genetic code during translation. rRNA (ribosomal RNA): it plays a structural and catalytic role during translation.What is the history of circular RNA? ›
Circular RNAs (circRNAs) were first found in pathogens. In 1976, Sanger et al (1976) described viroids that contain “single‐stranded and covalently closed circular RNA molecules”.Which has circular single-stranded DNA? ›
Circular single-stranded DNA viruses infect archaea, bacteria, and eukaryotic organisms.Is circular DNA single-stranded? ›
Single-stranded circular DNA (circDNA) are a class of single-stranded DNAs (ssDNA) featured with their covalently-closed topology.What is circular DNA called? ›
A plasmid is a small circular DNA molecule found in bacteria and some other microscopic organisms. Plasmids are physically separate from chromosomal DNA and replicate independently.
Circular DNA is a form of closed-loop DNA that has no ends. This type of DNA is found in the cytoplasm of most prokaryotic cells. Also, it is seen in organelles like chloroplasts and mitochondria. The plasmid DNA is a classic example of extrachromosomal circular DNA.Where is RNA round in a cell? ›
The nucleolus is a spherical structure found in the cell's nucleus whose primary function is to produce and assemble the cell's ribosomes. The nucleolus is also where ribosomal RNA genes are transcribed.