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Biomolecules
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Circular RNAs: Functions, Applications and Prospects
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Circular RNAs: Functions, Applications and Prospects

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Nucleic Acids".

Deadline for manuscript submissions: closed (20 August 2023) | Viewed by 17513

Special Issue Editors

Dr. William W. Du

E-Mail Website
Guest Editor
Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
Interests: circular RNAs functions and applications
Special Issues, Collections and Topics in MDPI journals
Dr. Feiya Li

E-Mail Website
Guest Editor
Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
Interests: circular RNAs functions and modes of actions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Circular RNAs (circRNAs) are a large class of noncoding RNAs generated from a process called back-splicing. They possess critical regulatory functions in many cellular events. Extensive circRNA functions and the underlying mechanisms have recently been reported, including sponging miRNA, exerting transcriptional and translational regulation, interacting with proteins, and translating into peptides and proteins. The dysregulation of these molecules has been implicated in many diseases.

The focus of this Special Issue of Biomolecules will be on discussing new functions of circular RNAs in various diseases and prospecting their potentials as biomarkers and therapeutic targets. The most recent advances in describing functions, functional mechanisms, and limitations of current circular RNA studies are encouraged. New strategies for researching circular RNA functions will be included. We encourage papers that describe challenges in using circRNAs as diagnostic and therapeutic tools, as well as those that propose future research directions. While research articles are the main focus of this Special Issue, review articles with overviews and novel perspectives regarding the future direction of the field are welcome.

Dr. William W. Du
Dr. Feiya Li
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • circular RNAs
  • circRNA
  • function
  • application
  • disease

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Related Special Issue

Published Papers (7 papers)

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Research

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18 pages, 10864 KiB  
Article
Presenilin-1-Derived Circular RNAs: Neglected Epigenetic Regulators with Various Functions in Alzheimer’s Disease
by Nima Sanadgol, Javad Amini, Cordian Beyer and Adib Zendedel
Biomolecules 2023, 13(9), 1401; https://doi.org/10.3390/biom13091401 - 17 Sep 2023
Cited by 1 | Viewed by 2265
Abstract
The presenilin-1 (PSEN1) gene is crucial in developing Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the most common cause of dementia. Circular RNAs (circRNAs) are non-coding RNA generated through back-splicing, resulting in a covalently closed circular molecule. This study aimed to investigate [...] Read more.
The presenilin-1 (PSEN1) gene is crucial in developing Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the most common cause of dementia. Circular RNAs (circRNAs) are non-coding RNA generated through back-splicing, resulting in a covalently closed circular molecule. This study aimed to investigate PSEN1-gene-derived circular RNAs (circPSEN1s) and their potential functions in AD. Our in silico analysis indicated that circPSEN1s (hsa_circ_0008521 and chr14:73614502-73614802) act as sponge molecules for eight specific microRNAs. Surprisingly, two of these miRNAs (has-mir-4668-5p and has-mir-5584-5p) exclusively interact with circPSEN1s rather than mRNA-PSEN1. Furthermore, the analysis of pathways revealed that these two miRNAs predominantly target mRNAs associated with the PI3K-Akt signaling pathway. With sponging these microRNAs, circPSEN1s were found to protect mRNAs commonly targeted by these miRNAs, including QSER1, BACE2, RNF157, PTMA, and GJD3. Furthermore, the miRNAs sequestered by circPSEN1s have a notable preference for targeting the TGF-β and Hippo signaling pathways. We also demonstrated that circPSEN1s potentially interact with FOXA1, ESR1, HNF1B, BRD4, GATA4, EP300, CBX3, PRDM9, and PPARG proteins. These proteins have a prominent preference for targeting the TGF-β and Notch signaling pathways, where EP300 and FOXA1 have the highest number of protein interactions. Molecular docking analysis also confirms the interaction of these hub proteins and Aβ42 with circPSEN1s. Interestingly, circPSEN1s-targeted molecules (miRNAs and proteins) impacted TGF-β, which served as a shared signaling pathway. Finally, the analysis of microarray data unveiled distinct expression patterns of genes influenced by circPSEN1s (WTIP, TGIF, SMAD4, PPP1CB, and BMPR1A) in the brains of AD patients. In summary, our findings suggested that the interaction of circPSEN1s with microRNAs and proteins could affect the fate of specific mRNAs, interrupt the function of unique proteins, and influence cell signaling pathways, generally TGF-β. Further research is necessary to validate these findings and gain a deeper understanding of the precise mechanisms and significance of circPSEN1s in the context of AD. Full article
(This article belongs to the Special Issue Circular RNAs: Functions, Applications and Prospects)
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20 pages, 14663 KiB  
Article
Identification and Characterization of circRNAs in Non-Lactating Dairy Goat Mammary Glands Reveal Their Regulatory Role in Mammary Cell Involution and Remodeling
by Rong Xuan, Jianmin Wang, Qing Li, Yanyan Wang, Shanfeng Du, Qingling Duan, Yanfei Guo, Peipei He, Zhibin Ji and Tianle Chao
Biomolecules 2023, 13(5), 860; https://doi.org/10.3390/biom13050860 - 18 May 2023
Cited by 2 | Viewed by 1855
Abstract
This study conducted transcriptome sequencing of goat-mammary-gland tissue at the late lactation (LL), dry period (DP), and late gestation (LG) stages to reveal the expression characteristics and molecular functions of circRNAs during mammary involution. A total of 11,756 circRNAs were identified in this [...] Read more.
This study conducted transcriptome sequencing of goat-mammary-gland tissue at the late lactation (LL), dry period (DP), and late gestation (LG) stages to reveal the expression characteristics and molecular functions of circRNAs during mammary involution. A total of 11,756 circRNAs were identified in this study, of which 2528 circRNAs were expressed in all three stages. The number of exonic circRNAs was the largest, and the least identified circRNAs were antisense circRNAs. circRNA source gene analysis found that 9282 circRNAs were derived from 3889 genes, and 127 circRNAs’ source genes were unknown. Gene Ontology (GO) terms, such as histone modification, regulation of GTPase activity, and establishment or maintenance of cell polarity, were significantly enriched (FDR < 0.05), which indicates the functional diversity of circRNAs’ source genes. A total of 218 differentially expressed circRNAs were identified during the non-lactation period. The number of specifically expressed circRNAs was the highest in the DP and the lowest in LL stages. These indicated temporal specificity of circRNA expression in mammary gland tissues at different developmental stages. In addition, this study also constructed circRNA–miRNA–mRNA competitive endogenous RNA (ceRNA) regulatory networks related to mammary development, immunity, substance metabolism, and apoptosis. These findings help understand the regulatory role of circRNAs in mammary cell involution and remodeling. Full article
(This article belongs to the Special Issue Circular RNAs: Functions, Applications and Prospects)
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Review

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19 pages, 3900 KiB  
Review
Circular RNA Expression Profiling by Microarray—A Technical and Practical Perspective
by Yanggu Shi and Jindong Shang
Biomolecules 2023, 13(4), 679; https://doi.org/10.3390/biom13040679 - 17 Apr 2023
Cited by 4 | Viewed by 2239
Abstract
Circular RNAs, as covalently circularized RNA loops, have many unique biochemical properties. Many circRNA biological functions and clinical indications are being continually discovered. Increasingly, circRNAs are being used as a new class of biomarkers, which are potentially superior to linear RNAs due to [...] Read more.
Circular RNAs, as covalently circularized RNA loops, have many unique biochemical properties. Many circRNA biological functions and clinical indications are being continually discovered. Increasingly, circRNAs are being used as a new class of biomarkers, which are potentially superior to linear RNAs due to the unusual cell/tissue/disease specificities and the exonuclease-resistant stabilized circular form in the biofluids. Profiling circRNA expression has been a common step in circRNA research to provide much needed insight into circRNA biology and to facilitate rapid advances in the circRNA field. We will review circRNA microarrays as a practical and effective circRNA profiling technology for regularly equipped biological or clinical research labs, share valuable experiences, and highlight the significant findings from the profiling studies. Full article
(This article belongs to the Special Issue Circular RNAs: Functions, Applications and Prospects)
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14 pages, 1368 KiB  
Review
The Essentials on microRNA-Encoded Peptides from Plants to Animals
by Mélanie Ormancey, Patrice Thuleau, Jean-Philippe Combier and Serge Plaza
Biomolecules 2023, 13(2), 206; https://doi.org/10.3390/biom13020206 - 19 Jan 2023
Cited by 10 | Viewed by 3073
Abstract
Primary transcripts of microRNAs (pri-miRNAs) were initially defined as long non-coding RNAs that host miRNAs further processed by the microRNA processor complex. A few years ago, however, it was discovered in plants that pri-miRNAs actually contain functional open reading frames (sORFs) that translate [...] Read more.
Primary transcripts of microRNAs (pri-miRNAs) were initially defined as long non-coding RNAs that host miRNAs further processed by the microRNA processor complex. A few years ago, however, it was discovered in plants that pri-miRNAs actually contain functional open reading frames (sORFs) that translate into small peptides called miPEPs, for microRNA-encoded peptides. Initially detected in Arabidopsis thaliana and Medicago truncatula, recent studies have revealed the presence of miPEPs in other pri-miRNAs as well as in other species ranging from various plant species to animals. This suggests that miPEP numbers remain largely underestimated and that they could be a common signature of pri-miRNAs. Here we present the most recent advances in miPEPs research and discuss how their discovery has broadened our vision of the regulation of gene expression by miRNAs, and how miPEPs could be interesting tools in sustainable agriculture or the treatment of certain human diseases. Full article
(This article belongs to the Special Issue Circular RNAs: Functions, Applications and Prospects)
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25 pages, 721 KiB  
Review
Non-Coding RNAs in the Regulation of Hippocampal Neurogenesis and Potential Treatment Targets for Related Disorders
by Zhengye Tan, Wen Li, Xiang Cheng, Qing Zhu and Xinhua Zhang
Biomolecules 2023, 13(1), 18; https://doi.org/10.3390/biom13010018 - 22 Dec 2022
Cited by 5 | Viewed by 2465
Abstract
Non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, circRNAs, and piRNAs, do not encode proteins. Nonetheless, they have critical roles in a variety of cellular activities—such as development, neurogenesis, degeneration, and the response to injury to the nervous system—via protein translation, RNA splicing, gene activation, [...] Read more.
Non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, circRNAs, and piRNAs, do not encode proteins. Nonetheless, they have critical roles in a variety of cellular activities—such as development, neurogenesis, degeneration, and the response to injury to the nervous system—via protein translation, RNA splicing, gene activation, silencing, modifications, and editing; thus, they may serve as potential targets for disease treatment. The activity of adult neural stem cells (NSCs) in the subgranular zone of the hippocampal dentate gyrus critically influences hippocampal function, including learning, memory, and emotion. ncRNAs have been shown to be involved in the regulation of hippocampal neurogenesis, including proliferation, differentiation, and migration of NSCs and synapse formation. The interaction among ncRNAs is complex and diverse and has become a major topic within the life science. This review outlines advances in research on the roles of ncRNAs in modulating NSC bioactivity in the hippocampus and discusses their potential applications in the treatment of illnesses affecting the hippocampus. Full article
(This article belongs to the Special Issue Circular RNAs: Functions, Applications and Prospects)
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14 pages, 601 KiB  
Review
Role of circRNA in E3 Modification under Human Disease
by Zishuo Chen, Minkai Song, Ting Wang, Jiawen Gao, Fei Lin, Hui Dai and Chao Zhang
Biomolecules 2022, 12(9), 1320; https://doi.org/10.3390/biom12091320 - 18 Sep 2022
Cited by 4 | Viewed by 2720
Abstract
Circular RNA (circRNA) is often regarded as a special kind of non-coding RNA, involved in the regulation mechanism of various diseases, such as tumors, neurological diseases, and inflammation. In a broad spectrum of biological processes, the modification of the 76-amino acid ubiquitin protein [...] Read more.
Circular RNA (circRNA) is often regarded as a special kind of non-coding RNA, involved in the regulation mechanism of various diseases, such as tumors, neurological diseases, and inflammation. In a broad spectrum of biological processes, the modification of the 76-amino acid ubiquitin protein generates a large number of signals with different cellular results. Each modification may change the result of signal transduction and participate in the occurrence and development of diseases. Studies have found that circRNA-mediated ubiquitination plays an important role in a variety of diseases. This review first introduces the characteristics of circRNA and ubiquitination and summarizes the mechanism of circRNA in the regulation of ubiquitination in various diseases. It is hoped that the emergence of circRNA-mediated ubiquitination can broaden the diagnosis and prognosis of the disease. Full article
(This article belongs to the Special Issue Circular RNAs: Functions, Applications and Prospects)
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Other

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22 pages, 3140 KiB  
Systematic Review
Circular RNAs and Their Role in Male Infertility: A Systematic Review
by Maria-Anna Kyrgiafini and Zissis Mamuris
Biomolecules 2023, 13(7), 1046; https://doi.org/10.3390/biom13071046 - 27 Jun 2023
Viewed by 1731
Abstract
Male infertility is a global health problem that is on the rise. Today, many noncoding RNAs (ncRNAs) are associated with male infertility. Circular RNAs (circRNAs) have recently drawn attention, but a comprehensive understanding of the role of circRNAs in male infertility is limited. [...] Read more.
Male infertility is a global health problem that is on the rise. Today, many noncoding RNAs (ncRNAs) are associated with male infertility. Circular RNAs (circRNAs) have recently drawn attention, but a comprehensive understanding of the role of circRNAs in male infertility is limited. This systematic review investigates the differential expression of circRNAs in male infertility or circRNAs that could serve as candidate biomarkers. The PRISMA guidelines were used to search PubMed and Web of Science on 11 January 2023. Inclusion criteria were human participants, experimental studies aiming to associate circRNAs with male infertility reporting differentially expressed circRNAs, and the English language. A total of 156 articles were found, and after the screening and eligibility stages, 13 studies were included in the final sample. Many circRNAs are deregulated in male infertility, and their interactions with miRNAs play an important role in affecting cellular processes and pathways. CircRNAs could also be used as biomarkers to screen patients before sperm retrieval. However, most studies focus on the role of circRNAs in azoospermia, and there is a knowledge gap regarding other subtypes of male infertility. Future research is needed to explore the exact mechanism of action of circRNAs and investigate their use as biomarkers. Full article
(This article belongs to the Special Issue Circular RNAs: Functions, Applications and Prospects)
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