Extensive translation of circular RNAs driven by N6-methyladenosine

Yang, Yun; Fan, Xiaojuan; Mao, Miaowei; Song, Xuehang; Wu, Ping; Zhang, Yang; Jin, Yongfeng; Yang, Yi; Chen, Ling Ling; Wang, Yang; Wong, Catherine C. L.; Xiao, Xinshu; Wang, Zefeng

doi:10.1038/cr.2017.31

Cited by 1,373 publications

(1,318 citation statements)

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“…The idea that translation of a circular RNA template in vitro is possible had been shown already in 1995 by Chen and Sarnow [5], using constructs with a so-called IRES element inserted (internal ribosome entry site) that promotes cap-independent translation. This situation changed with three publications that appeared concurrently in Cell Research [6] and Molecular Cell [7,8], applying different approaches, but coming to the same conclusion that, at least in some instances, endogenous circRNAs are in fact protein-coding.…”

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confidence: 99%

“…Yang et al [6] report in Cell Research that RNA base modification by N6-methyladenosine (m 6 A) provides an important signal mediating capindependent translation initiation on circRNAs. Their work is based on recent reports from several other groups that m 6 A modification is an important determinant for translation of canonical linear mRNAs and can even promote their cap-independent translation [9].…”

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confidence: 99%

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Circular RNAs: Coding or noncoding?

Schneider

Bindereif

2017

Cell Res

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confidence: 99%

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confidence: 99%

Circular RNAs: Coding or noncoding?

Schneider

Bindereif

2017

Cell Res

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“…• cytoplasm • generally formed by alternative splicing of pre-mRNA in which an upstream splice acceptor is joined to a downstream splice donor in a process known as 'backsplicing' (Barrett and Salzman 2016) • Expressed in thousands of human genes • Stable: half-life > 48 h • Expressed in a cell-type and tissue-specific manner • Act as miRNA sponges, interact with RNA binding proteins, can be positive regulators of their parental genes, • Can be translated (Yang, et al 2017c) • circRNAs were identified in human papillary thyroid cancer (Peng, et al 2017a) …”

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confidence: 99%

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

Klinge

2018

Endocrine-Related Cancer

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Abstract:The human genome is 'pervasively transcribed' leading to a complex array of noncoding RNAs (ncRNAs) that far outnumber coding mRNAs. ncRNAs have regulatory roles in transcription and post-transcriptional processes as well numerous cellular functions that remain to be fully described. Best characterized of the 'expanding universe' of ncRNAs are the ~ 22 nucleotide microRNAs (miRNAs) that base-pair to target mRNA's 3' untranslated region within the RNA-induced silencing complex (RISC) and block translation and may stimulate mRNA transcript degradation. Long non-coding RNAs (lncRNAs) are classified as >200 nucleotides in length, but range up to several kb and are heterogeneous in genomic origin and function.LncRNAs fold into structures that interact with DNA, RNA, and proteins to regulate chromatin dynamics, protein complex assembly, transcription, telomere biology, and splicing. Some lncRNAs act as sponges for miRNAs and decoys for proteins. Nuclear-encoded lncRNAs can be taken up by mitochondria and lncRNAs are transcribed from mtDNA. Both miRNAs and lncRNAs are dysregulated in endocrine cancers. This review provides an overview on the current understanding of the regulation and function of selected lncRNAs and miRNAs, and their interaction, in endocrine-related cancers: breast, prostate, endometrial, and thyroid.

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“…Interestingly, there is also some recent evidence that certain circRNAs can be translated, thus challenging the view that circRNAs belong to the family of noncoding RNAs [22][23][24].…”

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Circular RNA maps paving the road to biomarker development?

Görlach¹,

Holdenrieder

2017

J Mol Med

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In recent years, the RNAworld has gained increasing attention due to the discovery that in addition to the classical mRNAs, tRNAs, and rRNAs, various other functional mRNA forms exist including miRNAs, lncRNAs, piRNAs, siRNAs, tmRNAs, sRNAs, tiRNAs, eRNAs, snoRNAs, snRNAs, and other non-coding RNAs, which seem to play various roles under physiological and pathophysiological conditions. In particular, miRNAs have now been acknowledged to be of importance in many disease pathologies and are now being considered as diagnostic and even therapeutic tools.A recent addition to this family of diverse RNA molecules is the increasing number of various forms of circular RNAs (circRNAs). Although the presence of circular RNAs has already been noticed several decades ago in eukaryotes [1], they have been considered for a long time as transcriptional noise [2]. The extensive use of next-generation sequencing technologies together with advanced bioinformatic approaches has shown the presence of an abundant number of this diverse class of RNA molecules in various cell lines and tissues and across different species [3] (Fig. 1).Most circRNAs are produced during the backsplicing of exons, introns, or both, a process which is generally catalyzed by either the spliceosomal machinery or by group I and II ribozymes or by exon skipping [4]. Unlike linear RNA, the 3′ and 5′ ends in circRNA normally present in an RNA molecule have been joined together, forming a covalently closed continuous loop with a backsplicing junction, which makes them distinguishable from their linear counterparts. The circular loop structure also prevents degradation by RNA exonucleases, thus rendering these molecules highly stable [5]. circRNAs can contain one to many exons, and/or introns, and multiple circRNAs can be produced from a single gene. Most circRNAs derived from exons tend to be localized in the cytoplasm although the mechanisms of nuclear export are not clarified [5,6]. circRNAs derived from introns, or exons and introns can be found in the nucleus [7].The expression of circRNAs is not tightly bound to the expression levels of the linear transcript from which the circRNA is derived, indicating that expression of circRNA is regulated and that the spliceosome must be able to discriminate between forward splicing, i.e., canonical linear splicing and backsplicing [8]. While the levels of many circRNAs are much lower than their linear transcripts, in other cases, circRNA levels surveil over linear transcript levels or are even the only RNA species detectable. In human fibroblasts, it was estimated that circRNAs were derived from approximately 14% of actively transcribed genes, and that for some genes, circRNAs were more abundant than the corresponding linear mRNAs [3]. Analyses of RNA-seq data from the ENCODE project indicated that approximately 7000 human circRNAs showed an abundance of at least 10% of the transcripts from the corresponding genomic loci [9].Key factors which seem to count for circRNA levels in cells and tissues are circRNA stability an...

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Extensive translation of circular RNAs driven by N6-methyladenosine

Cited by 1,373 publications

References 49 publications

Circular RNAs: Coding or noncoding?

Circular RNAs: Coding or noncoding?

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

Circular RNA maps paving the road to biomarker development?

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