The new function of circRNA: translation
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REVIEW ARTICLE
The new function of circRNA: translation Y. Shi1 · X. Jia1 · J. Xu1 Received: 29 December 2019 / Accepted: 1 May 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020
Abstract Circular RNAs (circRNAs) have been considered a special class of non-coding RNAs without 5′ caps and 3′ tails which are covalently closed RNA molecules generated by back splicing of mRNA. For a long time, circRNAs have been considered to be directly involved in various biological processes as functional RNA. In recent years, a variety of circRNAs have been found to have translational functions, and the resultant peptides also play biological roles in the emergence and progression of human disease. The discovery of these circRNAs and their encoded peptides has enriched genomics, helped us to study the causes of diseases, and promoted the development of biotechnology. The purpose of this review is to summarize the research progress of the detection methods, translation initiation mechanism, as well as functional mechanism of peptides encoded by circRNAs, with the goal of providing the directions for the discovery of biomarkers for diagnosis, prognosis, and therapeutic targets for human disease. Keywords Circular RNA · Translation · Peptides · Functions Abbreviations circRNA Circular RNA IRES Internal ribosome entry site ORF Open reading frame eIF Eukaryotic initiation factor m6A N6-methyladenosine YTHDF1/2/3 YTH domain family protein 1/2/3 GFP Green fluorescent protein Rluc Rellina luciferase Luc Luciferase PCNA Proliferating cell nuclear antigen USP28 Ubiquitin-specific protease 28 GSK3β Glycogen synthase kinase 3 beta AKT3 Protein kinase B γ PDK1 Pyruvate dehydrogenase kinase isozyme 1 YAP1 Yes-associated protein 1 PAF1 Polymerase-associated factor GPCR G-protein-coupled receptor
* X. Jia [email protected] * J. Xu [email protected] 1
Department of Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, No.123, Tianfei Xiang, Mochou Road, Nanjing 210004, China
Rspo R-spondins METTL3/14 Methyltransferase-like 3/14 FTO Fat mass and obesity-associated protein ALKBH5 ALKB homolog 5 IME Intron-mediated enhancement
Introduction CircRNAs are generated from mRNAs via spliceosomemediated back splicing: the 3′ splicing site is covalently linked to the 5′ splicing site [1, 2]. CircRNAs were first documented in plant viroids in 1976 [3]. They are characteristically stabile, abundant, and conserved [4, 5]. Depending on the genome origin and mode of generation, circRNAs can be roughly divided into three types: intronic circRNAs [6, 7], exonic circRNAs [7, 8], and exon–intron circRNAs [9]. In the past few years, studies of their ability to cis-regulate parent genes [9–11], bind to miRNAs [12–14], bind to and form functional complexes with proteins [15–17] have suggested that circRNAs a critical role in eukaryotic cells. In 1995, circRNAs were found to synthesize long repeating polypeptide chains based on a continuous open reading frame, but
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