Detecting and characterizing circular RNAs

By William R. Jeck, N. Sharpless. Nature Biotechnology, 2014

2,405 citations recorded by the source corpus.

Circular RNA transcripts were first identified in the early 1990s but knowledge of these species has remained limited, as their study through traditional methods of RNA analysis has been difficult. Now, novel bioinformatic approaches coupled with biochemical enrichment strategies and deep sequencing have allowed comprehensive studies of circular RNA species. Recent studies have revealed thousands of endogenous circular RNAs in mammalian cells, some of which are highly abundant and evolutionarily conserved. Evidence is emerging that some circRNAs might regulate microRNA (miRNA) function, and roles in transcriptional control have also been suggested. Therefore, study of this class of noncoding RNAs has potential implications for therapeutic and research applications. We believe the key future challenge for the field will be to understand the regulation and function of these unusual molecules.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/095b6b5182065f1c661160268dcdfc75d3c26eaa

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Citations in the corpus

Circular RNA Expression: Its Potential Regulation and Function (2016, methodology): “In 2012, a statistical analysis of RNA-Seq data and subsequent biochemical analysis revealed a complete surprise: circRNA (see Glossary) molecules transcribed and spliced from exons in protein and noncoding genes are ubiquitous in the human and mouse genomes and, thus, are likely to be a pervasive a”
Comparison of circular RNA prediction tools (2015, background): “…circRNAs have evaded recognition or simply been discarded as artefacts during standard processing, which involves alignment to the ‘linear’ genome (9). circRNA are all characterized by a non-linear ‘back-splicing’ event between a splice donor (SD) and an up-stream splice acceptor (SA) in contrast…”
The bioinformatics toolbox for circRNA discovery and analysis (2020, background): “As early as 2014, the nomenclature for circRNA was discussed [3], although each database tends to create a unique system to represent circRNA genes.”
The RNA binding protein quaking regulates formation of circRNAs. (2015, positive): “Lacking 30 termini, circRNAs are non-polyadenylated and resistant to digestion of the RNAwith RNase R, a highly processive 30 exonuclease that non-specifically degrades linear RNA, but not circRNAs, attributes which are exploited in their sequencing and identification (Jeck and Sharpless, 2014).”
Genomewide analysis of Drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation (2014, positive): “Known circular RNAs are typically flanked by GT/AG splice sites reflecting back-splicing (Jeck and Sharpless, 2014).”
CSCD: a database for cancer-specific circular RNAs (2017, background): “Circular RNA (circRNA) is largely discovered by highthroughput sequencing (1), including many tissue-specific and cell-specific circRNAs (2,3).”
CircNet: a database of circular RNAs derived from transcriptome sequencing data (2015, neutral): “suggestions in 2014 Nature Reviews (48), we designed a circRNA naming system which provides information regarding source genes, whether the circRNA is antisense or intronic, and whether the back splice junction site is exactly located on well annotated exons.”
CIRI: an efficient and unbiased algorithm for de novo circular RNA identification (2015, background): “On the other hand, other natural or artificial mechanisms can also produce junction-like reads [15].”
Regulation of circRNA biogenesis (2015, methodology): “Two models have been proposed to explain the underlying mechanism of back-spliced circularization.(11,16,18,20,28) Broadly speaking, the notable difference between these 2 models is which step, canonical splicing or back-splicing, happens first (Fig.”
Detecting circular RNAs: bioinformatic and experimental challenges (2016, background): “…rate due to the biochemical variability of RNase R. qPCR validation has shown that some experimentally validated circRNAs are depleted by RNase R, including human CDR1as , a CAMSAP1 isoform with intron retention, MAN1A2 , NCX1 and Drosophila melanogaster Pangolin and Ank2 (REFS 3,4,7,26,57) .”
Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis (2017, background): “Nevertheless, genome-wide studies have demonstrated that miRNA sponging activity cannot be generally applied (Memczak et al., 2013; You et al., 2015; Jeck and Sharpless, 2014), and other mechanisms have also been proposed, such as acting as platforms for protein interaction (Hentze and Preiss, 2013)”
Single-cell transcriptome sequencing: recent advances and remaining challenges (2016, methodology): “Consequently, current methods are ill suited to investigate non-polyadenylated transcript classes, such as regulatory non-coding RNA (e.g. microRNAs 46,47 , lncRNAs 48 , or circular RNAs 49,50 ) or bacterial RNA 21 .”