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Non-coding RNA in Physiology and Pathophysiology

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 10 June 2024 | Viewed by 7874

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Special Issue Editors

Dr. Francesca Forini

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Guest Editor

CNR Institute of Clinical Physiology, Via G.Moruzzi 1, 56100 Pisa, Italy
Interests: molecular mechanisms in cardiovascular disease, diabetic retinopathy; idiopathic pulmonary hypertension, thyroid/heart axis; mitochondria physiology and pathophysiology; non coding RNA, animal models
Special Issues, Collections and Topics in MDPI journals

Dr. Manuela Cabiati

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Guest Editor

CNR Institute of Clinical Physiology, Via G.Moruzzi 1, 56100 Pisa, Italy
Interests: identification of new genes involved in cardiometabolic disease (heart failure, myocardial infarction, childhood obesity and diabetes) and cancer; expression studies of coding and non-coding RNA in in vitro, ex vivo and in vivo experimental models; development of analytical methods for the measurement of new biohumoral markers of disease

Dr. Giuseppina Nicolini

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Guest Editor

CNR Institute of Clinical Physiology, Via G.Moruzzi 1, 56100 Pisa, Italy
Interests: post-ischemic cardiac remodeling; pre-clinical animal models; signaling pathways; miRNA/gene regulatory networks
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Non-coding RNAs (ncRNAs) are a class of non-protein-coding transcripts widely expressed in mammalian cells with a tissue- and cell-specific distribution pattern. High-throughput RNA-sequencing technology revealed the key role played by ncRNAs as developmental and evolutionary determinants of organismal complexity. NcRNA mainly includes microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). Among small ncRNAs, miRNAs are capable of post-transcriptionally regulating many targets, thus fine-tuning a wide range of cellular pathways. Long ncRNAs can, in turn, regulate miRNAs’ expression and control gene transcription, pre-mRNA processing, the transport of mature mRNAs to specific cellular compartments, the regulation of mRNA stability, and protein translation and turnover. CircRNAs are single-stranded, covalently closed RNA molecules that exert biological functions by acting as transcriptional regulators, miRNA sponges, and protein templates.

In recent decades, the dysregulation of ncRNAs has been implicated in a wide variety of pathological conditions, especially senescence and degenerative disease such as cardiometabolic disease, cancer, and neurodegenerative disorders. The functions of ncRNAs in pathogenesis are unique for each disorder, as are the pertinent networks of ncRNA/miRNA/mRNA that mediate these functions. Thus, further understanding ncRNA biogenesis, release, and effects may aid the discovery of diagnostic biomarkers or the development of effective therapeutics for degenerative and age-related diseases affecting modern society.

The aim of this Special Issue is to collect novel findings on molecular mechanisms related to ncRNA function in physiological and pathological conditions. Topics on emerging targets for the implementation of innovative therapeutic strategies are also encouraged. Original research articles, up-to-date reviews, and commentaries are all welcome.

Dr. Francesca Forini
Dr. Manuela Cabiati
Dr. Giuseppina Nicolini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

microRNA
long non-coding RNA
circular RNA
epigenetics
cardiovascular disease
metabolic disease
nervous system disorders
cancer
aging

Published Papers (5 papers)

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Research

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22 pages, 6051 KiB

Open AccessArticle

Investigating the Differential Circulating microRNA Expression in Adolescent Females with Severe Idiopathic Scoliosis: A Proof-of-Concept Observational Clinical Study

by Lavinia Raimondi, Angela De Luca, Alessia Gallo, Fabrizio Perna, Nicola Cuscino, Aurora Cordaro, Viviana Costa, Daniele Bellavia, Cesare Faldini, Simone Dario Scilabra, Gianluca Giavaresi and Angelo Toscano

Int. J. Mol. Sci. 2024, 25(1), 570; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25010570 - 01 Jan 2024

Viewed by 1155

Abstract

Adolescent Idiopathic Scoliosis (AIS) is the most common form of three-dimensional spinal disorder in adolescents between the ages of 10 and 18 years of age, most commonly diagnosed in young women when severe disease occurs. Patients with AIS are characterized by abnormal skeletal growth and reduced bone mineral density. The etiology of AIS is thought to be multifactorial, involving both environmental and genetic factors, but to date, it is still unknown. Therefore, it is crucial to further investigate the molecular pathogenesis of AIS and to identify biomarkers useful for predicting curve progression. In this perspective, the relative abundance of a panel of microRNAs (miRNAs) was analyzed in the plasma of 20 AIS patients and 10 healthy controls (HC). The data revealed a significant group of circulating miRNAs dysregulated in AIS patients compared to HC. Further bioinformatic analyses evidenced a more restricted expression of some miRNAs exclusively in severe AIS females. These include some members of the miR-30 family, which are considered promising regulators for treating bone diseases. We demonstrated circulating extracellular vesicles (EVs) from severe AIS females contained miR-30 family members and decreased the osteogenic differentiation of mesenchymal stem cells. Proteomic analysis of EVs highlighted the expression of proteins associated with orthopedic disease. This study provides preliminary evidence of a miRNAs signature potentially associated with severe female AIS and suggests the corresponding vesicular component may affect cellular mechanisms crucial in AIS, opening the scenario for in-depth studies on prognostic differences related to gender and grade. Full article

(This article belongs to the Special Issue Non-coding RNA in Physiology and Pathophysiology)

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14 pages, 9658 KiB

Open AccessArticle

Comprehensive Pan-Cancer Mutation Density Patterns in Enhancer RNA

by Troy Zhang, Hui Yu, Limin Jiang, Yongsheng Bai, Xiaoyi Liu and Yan Guo

Int. J. Mol. Sci. 2024, 25(1), 534; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25010534 - 30 Dec 2023

Cited by 3 | Viewed by 796

Abstract

Significant advances have been achieved in understanding the critical role of enhancer RNAs (eRNAs) in the complex field of gene regulation. However, notable uncertainty remains concerning the biology of eRNAs, highlighting the need for continued research to uncover their exact functions in cellular processes and diseases. We present a comprehensive study to scrutinize mutation density patterns, mutation strand bias, and mutation burden in eRNAs across multiple cancer types. Our findings reveal that eRNAs exhibit mutation strand bias akin to that observed in protein-coding RNAs. We also identified a novel pattern, in which mutation density is notably diminished around the central region of the eRNA, but conspicuously elevated towards both the beginning and end. This pattern can be potentially explained by a mechanism involving heightened transcriptional activity and the activation of transcription-coupled repair. The central regions of the eRNAs appear to be more conserved, hinting at a potential mechanism preserving their structural and functional integrity, while the extremities may be more susceptible to mutations due to increased exposure. The evolutionary trajectory of this mutational pattern suggests a nuanced adaptation in eRNAs, where stability at their core coexists with flexibility at their extremities, potentially facilitating their diverse interactions with other genetic entities. Full article

(This article belongs to the Special Issue Non-coding RNA in Physiology and Pathophysiology)

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19 pages, 3940 KiB

Open AccessArticle

Depletion of SNORA33 Abolishes ψ of 28S-U4966 and Affects the Ribosome Translational Apparatus

by Alzbeta Chabronova, Guus van den Akker, Bas A. C. Housmans, Marjolein M. J. Caron, Andy Cremers, Don A. M. Surtel, Mandy J. Peffers, Lodewijk W. van Rhijn, Virginie Marchand, Yuri Motorin and Tim J. M. Welting

Int. J. Mol. Sci. 2023, 24(16), 12578; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241612578 - 08 Aug 2023

Cited by 1 | Viewed by 1192

Abstract

Eukaryotic ribosomes are complex molecular nanomachines translating genetic information from mRNAs into proteins. There is natural heterogeneity in ribosome composition. The pseudouridylation (ψ) of ribosomal RNAs (rRNAs) is one of the key sources of ribosome heterogeneity. Nevertheless, the functional consequences of ψ-based ribosome heterogeneity and its relevance for human disease are yet to be understood. Using HydraPsiSeq and a chronic disease model of non-osteoarthritic primary human articular chondrocytes exposed to osteoarthritic synovial fluid, we demonstrated that the disease microenvironment is capable of instigating site-specific changes in rRNA ψ profiles. To investigate one of the identified differential rRNA ψ sites (28S-ψ4966), we generated SNORA22 and SNORA33 KO SW1353 cell pools using LentiCRISPRv2/Cas9 and evaluated the ribosome translational capacity by ³⁵S-Met/Cys incorporation, assessed the mode of translation initiation and ribosomal fidelity using dual luciferase reporters, and assessed cellular and ribosomal proteomes by LC-MS/MS. We uncovered that the depletion of SNORA33, but not SNORA22, reduced 28S-ψ4966 levels. The resulting loss of 28S-ψ4966 affected ribosomal protein composition and function and led to specific changes in the cellular proteome. Overall, our pioneering findings demonstrate that cells dynamically respond to disease-relevant changes in their environment by altering their rRNA pseudouridylation profiles, with consequences for ribosome function and the cellular proteome relevant to human disease. Full article

(This article belongs to the Special Issue Non-coding RNA in Physiology and Pathophysiology)

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15 pages, 2214 KiB

Open AccessArticle

Evaluation of Exosomal Coding and Non-Coding RNA Signature in Obese Adolescents

by Manuela Cabiati, Emioli Randazzo, Letizia Guiducci, Alessandra Falleni, Antonella Cecchettini, Valentina Casieri, Giovanni Federico and Silvia Del Ry

Int. J. Mol. Sci. 2023, 24(1), 139; https://doi.org/10.3390/ijms24010139 - 21 Dec 2022

Cited by 4 | Viewed by 1190

Abstract

Exosomes may contribute to the pathogenesis of obesity through their action as communication mediators. As we have previously demonstrated, in obese adolescents, some circulating miRNAs modified the C-type natriuretic peptide (CNP) expression and were associated with changes in metabolic functions. At present no data are available on miRNA transport by exosomes in this condition. To verify and compare the presence and the expression of CNP/NPR-B/NPR-C, and some miRNAs (miR-33a-3p/miR-223-5p/miR-142-5p/miRNA-4454/miRNA-181a-5p/miRNA-199-5p), in circulating exosomes obtained from the same cohort of obese (O, n = 22) and normal-weight adolescents (N, n = 22). For the first time, we observed that exosomes carried CNP and its specific receptors only randomly both in O and N, suggesting that exosomes are not important carriers for the CNP system. On the contrary, exosomal miRNAs resulted ubiquitously and differentially expressed in O and N. O showed a significant decrease (p < 0.01) in the expression of all miRNAs except for miR-4454 and miR-142-5p. We have found significant correlations among miRNAs themselves and with some inflammatory/metabolic factors of obesity. These relationships may help in finding new biomarkers, allowing us to recognize, at an early stage, obese children and adolescents at high risk to develop the disease complications in adult life. Full article

(This article belongs to the Special Issue Non-coding RNA in Physiology and Pathophysiology)

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Review

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19 pages, 752 KiB

Open AccessReview

Functional Relationships between Long Non-Coding RNAs and Estrogen Receptor Alpha: A New Frontier in Hormone-Responsive Breast Cancer Management

by Viola Melone, Annamaria Salvati, Noemi Brusco, Elena Alexandrova, Ylenia D’Agostino, Domenico Palumbo, Luigi Palo, Ilaria Terenzi, Giovanni Nassa, Francesca Rizzo, Giorgio Giurato, Alessandro Weisz and Roberta Tarallo

Int. J. Mol. Sci. 2023, 24(2), 1145; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021145 - 06 Jan 2023

Cited by 4 | Viewed by 2383

Abstract

In the complex and articulated machinery of the human genome, less than 2% of the transcriptome encodes for proteins, while at least 75% is actively transcribed into non-coding RNAs (ncRNAs). Among the non-coding transcripts, those ≥200 nucleotides long (lncRNAs) are receiving growing attention for their involvement in human diseases, particularly cancer. Genomic studies have revealed the multiplicity of processes, including neoplastic transformation and tumor progression, in which lncRNAs are involved by regulating gene expression at epigenetic, transcriptional, and post-transcriptional levels by mechanism(s) that still need to be clarified. In breast cancer, several lncRNAs were identified and demonstrated to have either oncogenic or tumor-suppressive roles. The functional understanding of the mechanisms of lncRNA action in this disease could represent a potential for translational applications, as these molecules may serve as novel biomarkers of clinical use and potential therapeutic targets. This review highlights the relationship between lncRNAs and the principal hallmark of the luminal breast cancer phenotype, estrogen receptor α (ERα), providing an overview of new potential ways to inhibit estrogenic signaling via this nuclear receptor toward escaping resistance to endocrine therapy. Full article

(This article belongs to the Special Issue Non-coding RNA in Physiology and Pathophysiology)

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