Characterization of circular RNAs with advanced sequencing technologies in human complex diseases

Abstract

Circular RNAs (circRNAs) are one category of non‐coding RNAs that do not possess 5′ caps and 3′ free ends. Instead, they are derived in closed circle forms from pre‐mRNAs by a non‐canonical splicing mechanism named “back‐splicing.” CircRNAs were discovered four decades ago, initially called “scrambled exons.” Compared to linear RNAs, the expression levels of circRNAs are considerably lower, and it is challenging to identify circRNAs specifically. Thus, the biological relevance of circRNAs has been underappreciated until the advancement of next generation sequencing (NGS) technology. The biological insights of circRNAs, such as their tissue‐specific expression patterns, biogenesis factors, and functional effects in complex diseases, namely human cancers, have been extensively explored in the last decade. With the invention of the third generation sequencing (TGS) with longer sequencing reads and newly designed strategies to characterize full‐length circRNAs, the panorama of circRNAs in human complex diseases could be further unveiled. In this review, we first introduce the history of circular RNA detection. Next, we describe widely adopted NGS‐based methods and the recently established TGS‐based approaches capable of characterizing circRNAs in full‐length. We then summarize data resources and representative circRNA functional studies related to human complex diseases. In the last section, we reviewed computational tools and discuss the potential advantages of utilizing advanced sequencing approaches to a functional interpretation of full‐length circRNAs in complex diseases. This article is categorized under: RNA Evolution and Genomics > Computational Analyses of RNA RNA in Disease and Development > RNA in Disease

Computational approaches for circRNAs prediction andin silicocharacterization

“…It is worth noting that other publications in the literature have reviewed different aspects of the computational tools for circRNA identification and its in silico functional characterization (see [ 51 , 71 , 139 ]). However, unlike other reviews, our work offers a more accessible description of the most popular tools for circRNA identification, including technical aspects, as well as a compilation of the most popular tools for its in silico characterization in order to obtain functional insights of their biological roles.…”

“…Ruan et al (2022) [ 71 ] presented a comprehensive overview of different experimental strategies for full-length sequencing splicing variants detection of circRNAs. The authors summarize various library preparation techniques that enrich the sample for circRNAs and pipeline analysis using Oxford Nanopore Technology (ONT) sequencing.…”

Current advances in circular RNA detection and investigation methods: Are we running in circles?

“…Profiling by sequencing has become much more accessible in recent years, given the development of efficient bioinformatic tools for detecting circRNAs, which have been thoroughly described elsewhere (Chen et al, 2021;Rebolledo et al, 2023;Ruan et al, 2023). The novel tools can use previously reposited single and paired read total RNA-seq datasets to detect circRNAs (Nguyen et al, 2021(Nguyen et al, , 2022).…”

Structural characterizations of a unusual peptide CORO1C-47aa encoded by circRNA hsa-circ-0000437 associated with endometrial cancer

“…Recent studies have revealed that the circular RNA molecules take part in numerous cellular activities like, Gene Expressions, Sponging of miRNAs, and Binding to proteins for the regulatory purposes to name a few [1][2][3][4][5][6][7][8][9][10]. As a matter of surprise, some of the circular RNAs have been found to be able to code for peptides/proteins having a variety of functionalities [11][12][13][14][15].…”