Cellular functions of long noncoding rnas runw en y ao 1, 3, y ang wang 1,3 and lingling chen 1,2 a diverse catalog of long noncoding rnas lncrnas, which lack proteincoding potential, ar e. The formation of such circular intronic rnas cirnas can be recapitulated using expression vectors, and their processing depends on a consensus motif containing a 7 nt gurich element. Circular rnas circrnas are a novel class of rna molecules that form covalently closed loops capable of regulating gene expression at multiple levels. In addition to messenger rna mrna, cells contain diverse types of noncoding rna such as microrna mirna, small interfering rna sirna, trans. Circrnas are abundant and stably exist in creatures, and they are found with covalently closed loop structures in which they are quite different from linear rnas. In at least 2 cases cdr1ascirs7 and sry, circular rnas function to sponge speci. Short intronic repeat sequences facilitate circular rna production dongming liang and jeremy e. Circular rnas are mirna sponges and can be used as a new class of biomarker. Although their physiological functions are not yet completely defined, they are thought to control transcription, translation, and microrna levels. Identification and characterization of circular rnas in. The emerging landscape of circular rna in life processes.
In support of putative functions, gwas for cardiovascular diseases have shown predictive single. Circular rna new member of noncoding rna with novel functions article pdf available in experimental biology and medicine 24211. Additionally, others are derived from long primary transcripts with noncanonical rna. Being long intronic ncrnas, their transcripts are encoded within the introns of annotated genes. Widespread noncoding circular rnas in plants ye 2015. As such, these rnas are potential therapeutic targets and diagnostic markers for hcc. Long noncoding rnas in the regulation of gene expression mdpi. Short intronic repeat sequences facilitate circular rna. The diversity of long noncoding rnas and their generation. Circular rna or circrna is a type of singlestranded rna which, unlike the better known. Circrnas are generated in the process of backsplicing and can originate from di. Regulation of long noncoding rnas and circular rnas in.
The accumulating evidence indicate that circular rna circrna is a novel class of noncoding rna with diverse molecular functions. Most of these lariats are destroyed within minutes in the cell nucleus. The competitive endogenous rnas cernas contain shared mres, such as mrnas, pseudogenes, and long noncoding rnas lncrnas, and can compete for mirna binding. The length of most exonic circrnas is less than 1500 nt, the. This is a circular argument of dubious merit 45, since there is increasing evidence that.
Circrnas are abundant in eukaryotic transcripts and show certain levels of tissue and cell specificity. Exogenously overexpressed intronic long noncoding rnas. Circular rna expression profiles alter significantly in. Circular rnas circrnas play important roles in animals, plants, and fungi.
In 1996, circrnas were found to consist of exons from rna transcripts in. Noncoding rnas have emerged as important regulators of cardiac function and have been implicated in disease. Circrnas are a class of rna molecules that structurally form closed loops. Circular rnas circrnas are a large group of rnas that form covalently closed continuous loops. We then investigated the properties of plant circrnas, and revealed features similar to or distinct from that of animal circrnas. Long noncoding rnas lncrnas are emerging as potential key regulators in gene expression networks and exhibit a surprising range of shapes and sizes. As a novel class of long noncoding rnas, circular rnas circrnas are widely expressed in the tree of life 1,2,3. Author links open overlay panel yang zhang 1 3 xiaoou zhang 2 3 tian chen 1 jianfeng xiang 1 qingfei yin 1 yuhang xing 1 shanshan zhu 2 li yang 2 lingling chen 1.
Shortly after transcription, the intronic sequences are spliced out of the primary rna transcript as lariat rnas circular molecules with a short tail. Just a few years ago, it had been assumed that the dominant rna isoforms produced from eukaryotic genes were variants of messenger rna, functioning as intermediates in gene expression. Molecular mechanisms of circular rnas, transforming growth. While significant progress has been made in understanding the roles of micrornas and long noncoding rnas, the functional roles of circular rnas are less explored. Circular rnas circrnas were predicted to be the most abundant isoform compared to the. Request pdf circular intronic long noncoding rnas we describe the identification and characterization of circular intronic long noncoding rnas in human cells, which accumulate owing to a. Circular rnas circrnas are a class of noncoding rnas ncrnas that form covalently closed continuous loop structures, lacking the terminal 5. As with mouse blood, we separated rbcs from white cells on a percoll gradient. Circular rnas circrnas are a novel class of noncoding rnas formed from many proteincoding genes by backsplicing. Microprocessor mediates transcriptional termination of long noncoding rna transcripts hosting micrornas. By contrast, long ncrnas are typically greater than 200 nt, including long intergenic ncrnas, long intronic ncrnas, and. Zhang xo, chen t, xiang jf, yin qf, xing yh, et al.
Full text emerging roles of circular rnas in colorectal. We describe the identification and characterization of circular intronic long noncoding rnas in human cells, which accumulate owing to a failure in debranching. Noncoding rnas ncrnas can be divided into micrornas mirnas. Circular rna circrna, a novel type of endogenous noncoding rna ncrna, has become a research hotspot in recent years. Circular intronic rnas contain a single circularized intron and accumulate in the nucleus to regulate the gene. Pdf circular intronic long noncoding rnas ling yang. Circular rnas circrnas are a newly discovered class of endogenous noncoding rnas. Complementary sequencemediated exon circularization. Most of the circular rnas originate from the exon region of the encoded protein, and some are derived from intron regions, antisense transcripts, or long noncoding rnas. Circular intronic long noncoding rnas sciencedirect.
Moreover, alternative splicing can lead to the formation of circular rnas. Preeclampsia pe, a common hypertensive disorder of pregnancy, has a profound impact on maternal and neonatal mortality and morbidity. Circular rnas in cardiovascular diseases springerlink. Identification of circular intronic rnas a an example of identified intronic long noncoding rnas.
Due to lack of canonical export signals, circular rnas were thought to re ach the cytoplasm upon. Full text micrornas, long noncoding rnas, and circular rnas. Long noncoding rnas long ncrnas, lncrna are a type of rna, defined as being transcripts with lengths exceeding 200 nucleotides that are not translated into protein. Introns are noncoding dna sequences interspersed among the coding sequences of genes. They have been categorized as noncoding rna, but more recently, they have been shown. The formation of such circular intronic rnas cirnas can be recapitulated using expression vectors, and their processing depends on a consensus motif containing a 7 nt gurich element near the 5. Their unique circular structure makes circrnas more stable than linear rnas. The formation of such circular intronic rnas cirnas can be recapitulated using expression vectors, and their processing depends on a consensus motif containing a 7 nt gurich.
Nowadays, an increasing number of scientists have demonstrated that circrnas may have played an essential role. Structure, regulation, and function of linear and circular long non. Exogenously overexpressed intronic long noncoding rnas activate host gene expression by affecting histone modification in arabidopsis. Circular rnas circrnas are noncoding rnas characterized by circular covalently closed structures, which are generated by backsplicing. Molecular cell article circular intronic long noncoding rnas yangzhang, 1,3xiaoouzhang,2 tianchen, 1jianfengxiang, qingfeiyin, yuhangxing, shanshanzhu,2 liyang,2, and lingling chen1, 1state key laboratory of molecular biology, institute of biochemistry and cell biology 2key laboratory of computational biology, casmpg partner institute for computational biology. Circular rna new member of noncoding rna with novel. With the emergence of nextgeneration sequencing, especially rna sequencing technology, numerous circrnas have been found.
It is known that mirnas have been shown to be involved in nearly all aspects of cellular functions 42 and play important roles in disease initiation and progression, especially in. Circular rnas circrnas, a group of circular rna molecules with a 3. We report here that many such intronic rnas are, in fact, exported to the cytoplasm. Both stable lariats and circularized fulllength intronic rnas occur in human rbcs as well. In early 2012, however, a surprising discovery was made. Highthroughput analysisrevealed 143 circular intronic rnas similar to the two types of mouse sisrnas fig. Several distinct classes of lncrnas are transcribed from different dna elements, including promoters, enhancers, and intergenic regions in eukaryotic genomes. Circular rnas are naturally resistant to degradation by exonucleases and thus accumulate as stable transcripts. Wilusz department of biochemistry and biophysics, university of pennsylvania perelman school of medicine, philadelphia, pennsylvania 19104, usa recent deep sequencing studies have revealed thousands of circular noncoding rnas generated from protein. Long noncoding rnas lncrnas constitute a heterogenic class of rnas that includes, for example, intergenic lncrnas, antisense transcripts, and enhancer rnas. Circular rnas circrnas are a distinct class of newly discovered endogenous noncoding rnas salzman et al. Request pdf circular intronic long noncoding rnas we describe the identification and characterization of circular intronic long noncoding. However, no circrnas have been reported in ganoderma lucidum. In addition, small nucleolar lncrnas are flanked by small nucleolar rnas at both 3 and 5 ends, consequently resist degradation and accumulate.
Long noncoding rnas lncrnas, including linear lncrnas and. This feature confers numerous properties to circular rnas, many of which have only recently been identified. Circular rna or circrna is a type of singlestranded rna which, unlike the better known linear rna, forms a covalently closed continuous loop, i. Recent studies suggest that the majority of the human genome is transcribed, but only about 2% accounts for proteincoding exons. This somewhat arbitrary limit distinguishes long ncrnas from small noncoding rnas such as micrornas mirnas, small interfering rnas sirnas, piwiinteracting rnas pirnas, small nucleolar rnas snornas, and other short rnas. Researchers from the chinese academy of sciences describe the identification and characterization of circular intronic long noncoding rnas in human cells, which accumulate owing to a failure in debranching. Lariat intronic rnas in the cytoplasm of vertebrate cells. Circular rnas in human cancer molecular cancer full text. Although intronic or introncontaining circular rnas are retained in the nucleus 10,12, most circular rnas are efficiently exported to the cytoplasm,14. The first circrna was found in a rna virus in 1976 1, 2. Noncoding rnas ncrnas are a versatile group of rna transcripts without protein. The formation of such circular intronic rnas cirnas can be recapitulated using expression vectors, and their.