Repetitive elements regulate circular RNA biogenesis

Wilusz, Jeremy E.

doi:10.1080/2159256x.2015.1045682

Cited by 61 publications

(52 citation statements)

References 54 publications

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“…For example, circular RNA production from the Drosophila mbl gene is triggered when the Mbl splicing factor binds to its own introns (Ashwal-Fluss et al 2014). However, in humans, mice, and C. elegans, the predominant determinants of whether a pre-mRNA is subjected to backsplicing are intronic repetitive elements, such as sequences derived from transposons (for review, see Wilusz 2015). Almost 90% of human circular RNAs have complementary Alu elements in their flanking introns (Ivanov et al 2015), and, analogous to the protein-bridging mechanism, base-pairing between complementary sequences allows the intervening splice sites to be brought close together (Dubin et al 1995;Jeck et al 2013;Liang and Wilusz 2014;Zhang et al 2014;Ivanov et al 2015;Li et al 2015).…”

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confidence: 99%

Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins

et al. 2015

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Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons that circularize in Drosophila, but the underlying mechanisms by which these circular RNAs are generated are largely unknown. Here, using extensive mutagenesis of expression plasmids and RNAi screening, we reveal that circularization of the Drosophila laccase2 gene is regulated by both intronic repeats and trans-acting splicing factors. Analogous to what has been observed in humans and mice, basepairing between highly complementary transposable elements facilitates backsplicing. Long flanking repeats (∼400 nucleotides [nt]) promote circularization cotranscriptionally, whereas pre-mRNAs containing minimal repeats (<40 nt) generate circular RNAs predominately after 3 ′ end processing. Unlike the previously characterized Muscleblind (Mbl) circular RNA, which requires the Mbl protein for its biogenesis, we found that Laccase2 circular RNA levels are not controlled by Mbl or the Laccase2 gene product but rather by multiple hnRNP (heterogeneous nuclear ribonucleoprotein) and SR (serine-arginine) proteins acting in a combinatorial manner. hnRNP and SR proteins also regulate the expression of other Drosophila circular RNAs, including Plexin A (PlexA), suggesting a common strategy for regulating backsplicing. Furthermore, the laccase2 flanking introns support efficient circularization of diverse exons in Drosophila and human cells, providing a new tool for exploring the functional consequences of circular RNA expression across eukaryotes.

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Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins

et al. 2015

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“…Exon skipping is a common type of alternative splicing with a well-established impact in mRNA formation [42]. However, a recent study suggest that exon skipping may also have a pivotal role in ecircRNA biogenesis [40,41].…”

Section: Biogenesis Of Circrnasmentioning

confidence: 99%

Regulatory Role of Circular RNAs and Neurological Disorders

et al. 2016

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Circular RNAs (circRNAs) are a class of long noncoding RNAs that are characterized by the presence of covalently linked ends, and have been found in all life kingdoms. Exciting studies in regulatory roles of circRNAs are emerging. Here we summarize classification, characteristics, biogenesis and regulatory functions of circRNAs. CircRNAs are found to be preferentially expressed along neural genes and in neural tissues. We thus highlight the association of circRNA dysregulation with neurodegenerative diseases such as Alzheimer’s disease. Investigation of regulatory role of circRNAs will shed novel light in gene expression mechanisms during development and under disease conditions, and may identify circRNAs as new biomarkers for aging and neurodegenerative disorders.

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“…The circular intronic RNAs (ciRNAs) class is derived from lariat introns during canonical splicing; failure to debranch at the branch point site and trimming of the lariat tail leads to the formation of a stable ciRNA . CircRNAs have been reviewed in detail, focusing on their biogenesis, classification, and possible role in diseases, and have been cataloged in databases (Figure ) . In this review, we will highlight these aspects but will concentrate our discussion on new potential functions and considerations of these regulatory RNAs.…”

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confidence: 99%

Emerging roles and context of circular RNAs

et al. 2016

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Circular RNAs (CircRNAs) represent a large class of noncoding RNAs (ncRNAs) that have recently emerged as regulators of gene expression. They have been shown to suppress microRNAs, thereby increasing the translation and stability of targets of such microRNAs. In this review, we discuss the emerging functions of circRNAs, including RNA transcription, splicing, turnover, and translation. We also discuss other possible facets of circRNAs that can influence their function depending on the cell context, such as circRNA abundance, subcellular localization, interacting partners (RNA, DNA, and proteins), dynamic changes in interactions following stimulation, and potential circRNA translation. The ensuing changes in gene expression patterns elicited by circRNAs are proposed to drive key cellular processes, such as cell proliferation, differentiation and survival, that govern health and disease.

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Repetitive elements regulate circular RNA biogenesis

Cited by 61 publications

References 54 publications

Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins

Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins

Regulatory Role of Circular RNAs and Neurological Disorders

Emerging roles and context of circular RNAs

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