Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity

You, Xintian; Vlatkovic, Irena; Babić, Ana; Will, Tristan J.; Epstein, Irina; Tushev, Georgi; Akbalık, Güney; Wang, Mantian; Glock, Caspar; Quedenau, Claudia; Wang, Xi; Hou, Jingyi; Liu, Hongyu; Sun, Wei; Sambandan, Sivakumar; Chen, Tao; Schuman, Erin M.; Chen, Wei

doi:10.1038/nn.3975

Cited by 964 publications

(1,066 citation statements)

References 43 publications

Supporting

Mentioning

1,008

Contrasting

Unclassified

Order By: Relevance

“…9,13,15 circRNAs are upregulated overall during brain differentiation, 13 are highly enriched in synapses, 15 and are often differentially expressed compared to their mRNA isoforms, indicating that some of these circRNAs may have functions in the brain. CDR1as circRNA, one of the best known circRNAs, functions as an miR-7 sponge in neuronal tissues.…”

Section: Brain Development and Related Diseasementioning

confidence: 99%

“…[7][8][9][10] Specifically, a large number of circRNAs have been successfully identified in various cell lines and across different species. [11][12][13][14][15][16] Moreover, many circRNAs have been found to be expressed in a cell type-specific or tissue-specific manner, [13][14][15][16] suggesting they might have biological functions.…”

Section: Introductionmentioning

confidence: 99%

“…Genome-wide RNA-sequencing analyses have now identified a considerable number of circRNAs derived from backsplicing. Although they are generally expressed at low levels, increasing evidence has shown that circRNAs are linked to physiological development 15 and different diseases, such as neurological dystrophy, 21 cardiovascular diseases, [22][23][24][25] and cancer. [26][27][28] Recently, circRNAs have also been shown to be enriched and stable in plasma, 29 saliva, 30 and even in serum exosomes, 31 indicating the potential of circRNAs as readable biomarkers.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The emerging role and clinical implication of human exonic circular RNA

Lyu

Huang

2016

RNA Biology

View full text Add to dashboard Cite

Circular RNA from backspliced exons (or exonic circular RNA, circRNA) is a type of covalently closed noncolinear RNA that was recently rediscovered in eukaryotes. Although circRNAs are often expressed at low levels, emerging evidence indicates that many circRNAs are linked to physiological development and various diseases. Notably, circRNAs have been shown to serve as oncogenic stimuli or tumor suppressors in cancer. circRNAs may regulate gene expression through different mechanisms. In addition, circRNAs have been shown to be useful as biomarkers of diseases due to their stability, specific expression and relation to diseases both in cells and in extracellular fluid. This review summarizes current knowledge of human circRNAs and discusses the emerging role and clinical implication of these multifarious transcripts.

show abstract

Section: Brain Development and Related Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The emerging role and clinical implication of human exonic circular RNA

Lyu

Huang

2016

RNA Biology

View full text Add to dashboard Cite

show abstract

“…The phenomena that some circRNAs are cytoplasmic (e.g., CDR1as and circSry) and some are nuclear (e.g., EIciRNA) suggest strongly the existence of an active "transporting" or "sorting" mechanism for circRNAs. Interestingly, punctae of circRNAs are found in the neuronal dendrites [10], which is another indication for the involvement of special mechanism for circRNA subcellular localization.…”

mentioning

confidence: 86%

“…It is proposed that circRNAs may be "localized" passively to cytoplasm due to the breakdown of nuclear membrane during mitosis, although this cannot explain the cytoplasmic localization of most circRNAs in the non-dividing cells such as neurons [10]. The phenomena that some circRNAs are cytoplasmic (e.g., CDR1as and circSry) and some are nuclear (e.g., EIciRNA) suggest strongly the existence of an active "transporting" or "sorting" mechanism for circRNAs.…”

mentioning

confidence: 99%

Circular RNAs remain peculiarly unclear in biogenesis and function

Chen

2015

Sci. China Life Sci.

View full text Add to dashboard Cite

The known complexity of eukaryotic transcriptomes has been greatly expanded due to the identification of a large family of circular RNAs in recent years [13]. As a special form of RNA compared to the "common" linear form, these molecules were first described in 1976, when it was discovered that several plant viroids were single-stranded and covalently closed circular RNAs [4]. In a broad sense, the "circular" form RNAs may include viroids, genome of some RNA viruses, the loop portion of intronic lariats, as well as circular RNAs formed from back-splicing of exons. Currently in the field and also for this review, the term of circular RNA (circRNA) refers to circular molecules from back-splicing of exons unless specified.Thousands of circRNAs are now found in human cells and in model organisms such as mice, Drosophila, and C. elegans. A question coming out immediately is how these molecules are generated in cells. Biogenesis of certain circRNAs had long been linked to the relatively long introns and the complementary repeat sequences flanking the region of circularization [5][6][7]. Genome-wide bioinformatic analysis actually confirmed the association of these features to circRNA biogenesis [5][6][7]. The exonic sequences within the circRNAs might also be important in some cases [6,7]. At current stage, these associations are linked to the biogenesis of most but not all circRNAs, and are not connected with any actual molecular mechanism. There are also disputes about whether circRNAs are generated co-transcriptionally or post-transcriptionally [5,6]. A recent publication showed that the RNA-binding protein quaking I 5 (QKI5) might participate in the circularization [8], although we have to keep in mind with several points before considering QKI5 as an essential player in circRNA biogenesis. First, QKI5 is a known regulatory factor of alternative splicing for selective mRNAs. Presumably many factors participating in pre-mRNA splicing or alternative splicing may also get involved in back-splicing for the formation of circRNAs "non-specifically". One would wonder whether there is any protein "specific" for circRNA biogenesis. Secondly, circRNAs are wide-spread transcripts found essentially in all cell types examined. We would anticipate that essential factors for circRNA biogenesis are someway ubiquitously expressed, but QKI5 is not expressed in all cells. Thirdly, flanking complementary sequences are associated with more than half of the circRNAs, and QKI5 has not been tested for biogenesis of circRNAs with flanking complementary repeats [8]. Some circRNAs showed cell type or tissue specific expression between two cells under comparison, even when their parent genes might be expressed (as mRNA) in both cells [7]. The ratio of circRNAs to mRNAs for individual genes was also dynamic among different cells under different conditions. These indicate strongly that biogenesis of circRNAs must be regulated with gene and cell type specificity, and also argue against the idea that circRNAs may be unavoidable byproducts of sp...

show abstract

Biological functions, regulatory mechanisms, and disease relevance of RNA localization pathways

et al. 2018

View full text Add to dashboard Cite

The asymmetric subcellular distribution of RNA molecules from their sites of transcription to specific compartments of the cell is an important aspect of post-transcriptional gene regulation. This involves the interplay of intrinsic cis-regulatory elements within the RNA molecules with trans-acting RNAbinding proteins and associated factors. Together, these interactions dictate the intracellular localization route of RNAs, whose downstream impacts have wide-ranging implications in cellular physiology. In this review, we examine the mechanisms underlying RNA localization and discuss their biological significance. We also review the growing body of evidence pointing to aberrant RNA localization pathways in the development and progression of diseases.Keywords: Cis-regulatory elements; RNA disease; RNA localization; RNA-binding proteinsThe asymmetric organization of cells is a pervasive feature that ensures the homeostasis of prokaryotic and eukaryotic organisms. This relies on the capacity of cells to organize their contents, including lipids, nucleic acids, and proteins, into specific subcellular structures and organelles. While much of this organization has been attributed to subcellular protein transport [1], a growing body of work indicates that the regulated localization of RNA molecules is also a key process observed across evolutionary timescales [2][3][4][5][6]. This form of post-transcriptional regulation where coding and noncoding RNA molecules actively associate with trans-acting partners, such as RNA-binding proteins (RBPs), serves to dictate both the function and intra-or extracellular destiny of the RNA. During RNA localization, cis-regulatory elements found within the RNA molecule, whether coding or noncoding, act as recognition sites for the recruitment of trans-acting RBPs, which dictate the intra-/extra-cellular fate of the RNA and, ultimately, its functional state. Over the years, the wide-ranging implications of RNA localization on cellular physiology have become apparent, affecting many aspects of cell organization and function. Indeed, RNA localization pathways have been linked to numerous important processes, including developmental patterning, cell polarity, spindle assembly, formation of nonmembranous compartments, localized translation, and cell motility [2][3][4][5][6].

show abstract

Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity

Cited by 964 publications

References 43 publications

The emerging role and clinical implication of human exonic circular RNA

The emerging role and clinical implication of human exonic circular RNA

Circular RNAs remain peculiarly unclear in biogenesis and function

Biological functions, regulatory mechanisms, and disease relevance of RNA localization pathways

Contact Info

Product

Resources

About