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RNA Metabolism: Role in Human Pathophysiology and Its Potential for Therapeutic Interventions

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 14390

Special Issue Editors

Dr. Claudia Ghigna

E-Mail Website
Guest Editor
Institute of Molecular Genetics Luigi Luca Cavalli-Sforza, National Research Council, 27100 Pavia, Italy
Interests: alternative splicing; cancer; angiogenesis; vascular development; RNA binding proteins
Special Issues, Collections and Topics in MDPI journals
Dr. Laura Cerchia

E-Mail Website
Guest Editor
Institute of Experimental Endocrinology and Oncology “G. Salvatore” National Research Council (IEOS-CNR), 80131 Naples, Italy
Interests: nucleic acid aptamer; SELEX technology; tumor markers; targeted therapy; targeted drug delivery; cancer theranostics; cancer cell biology and signaling; chemotherapy resistance; tumor microenvironment; TNBC
Special Issues, Collections and Topics in MDPI journals
Dr. Laura Poliseno

E-Mail Website
Guest Editor
Oncogenomics Unit, Institute of Clinical Physiology (IFC), National Research Council (CNR), and Core Research Laboratory (CRL), Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), 56124 Pisa, Italy
Interests: melanoma; BRAFV600E isoforms; microRNAs; ceRNAs; pigmentation; melanoma modeling in zebrafish and mice; attenuated Listeria monocytogenes; pseudogenes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human cells display different types of RNA molecules. However, until a few years ago many of these RNA types were considered as “junk”. Instead, accumulating evidence indicates that RNA molecules are at the basis of the spatio-temporal organization of cellular functions in a number of physiological processes. From a mechanistic point of view, the transcription, processing, transport, and activity of these RNA molecules require a complex interplay between RNA sequence elements and RNA-binding proteins. Consequently, their characterization has provided a new perspective to understand the impact of the post-transcriptional regulation of gene expression in both establishing and maintaining fundamental properties of different cell and tissue types. 

Considering the functions and the elevated number of processes in which RNA molecules work, it is not surprising that errors of RNA metabolism are causatively linked to genetic disorders and are also involved in many more common chronic diseases, including cancer. Importantly, the multiple levels of RNA metabolism regulation offer the potential for therapeutic interventions which can be exploited in the future. 

The main goal of this Special Issue is to collect recent insights into: i. the mechanisms and functional roles of RNA molecules; ii. their alterations in human diseases; and iii. their manipulation for the development of innovative therapeutic strategies. We invite authors to contribute with original research articles or review articles that illustrate the state of the art in RNA metabolism and help to stimulate continuing efforts in this research field.

Dr. Claudia Ghigna
Dr. Laura Cerchia
Dr. Laura Poliseno
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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • RNA metabolism
  • post-transcriptional regulation of gene expression
  • RNA-binding proteins (RBPs)
  • RNA alterations
  • RNA therapy
  • delivery of RNA-based drugs
  • RNA modification

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Published Papers (3 papers)

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Research

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22 pages, 2617 KiB  
Article
Alternative Splicing Changes Promoted by NOVA2 Upregulation in Endothelial Cells and Relevance for Gastric Cancer
by Anna Di Matteo, Elisa Belloni, Davide Pradella, Anna Maria Chiaravalli, Giacomo Maria Pini, Mattia Bugatti, Roberta Alfieri, Chiara Barzan, Elena Franganillo Tena, Silvia Bione, Elisa Terenzani, Fausto Sessa, Christopher D. R. Wyatt, William Vermi and Claudia Ghigna
Int. J. Mol. Sci. 2023, 24(9), 8102; https://doi.org/10.3390/ijms24098102 - 30 Apr 2023
Cited by 5 | Viewed by 2638
Abstract
Angiogenesis is crucial for cancer progression. While several anti-angiogenic drugs are in use for cancer treatment, their clinical benefits are unsatisfactory. Thus, a deeper understanding of the mechanisms sustaining cancer vessel growth is fundamental to identify novel biomarkers and therapeutic targets. Alternative splicing [...] Read more.
Angiogenesis is crucial for cancer progression. While several anti-angiogenic drugs are in use for cancer treatment, their clinical benefits are unsatisfactory. Thus, a deeper understanding of the mechanisms sustaining cancer vessel growth is fundamental to identify novel biomarkers and therapeutic targets. Alternative splicing (AS) is an essential modifier of human proteome diversity. Nevertheless, AS contribution to tumor vasculature development is poorly known. The Neuro-Oncological Ventral Antigen 2 (NOVA2) is a critical AS regulator of angiogenesis and vascular development. NOVA2 is upregulated in tumor endothelial cells (ECs) of different cancers, thus representing a potential driver of tumor blood vessel aberrancies. Here, we identified novel AS transcripts generated upon NOVA2 upregulation in ECs, suggesting a pervasive role of NOVA2 in vascular biology. In addition, we report that NOVA2 is also upregulated in ECs of gastric cancer (GC), and its expression correlates with poor overall survival of GC patients. Finally, we found that the AS of the Rap Guanine Nucleotide Exchange Factor 6 (RapGEF6), a newly identified NOVA2 target, is altered in GC patients and associated with NOVA2 expression, tumor angiogenesis, and poor patient outcome. Our findings provide a better understanding of GC biology and suggest that AS might be exploited to identify novel biomarkers and therapeutics for anti-angiogenic GC treatments. Full article
(This article belongs to the Special Issue RNA Metabolism: Role in Human Pathophysiology and Its Potential for Therapeutic Interventions)
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Review

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18 pages, 1385 KiB  
Review
Reviewing the Potential Links between Viral Infections and TDP-43 Proteinopathies
by Zerina Rahic, Emanuele Buratti and Sara Cappelli
Int. J. Mol. Sci. 2023, 24(2), 1581; https://doi.org/10.3390/ijms24021581 - 13 Jan 2023
Cited by 8 | Viewed by 4117
Abstract
Transactive response DNA binding protein 43 kDa (TDP-43) was discovered in 2001 as a cellular factor capable to inhibit HIV-1 gene expression. Successively, it was brought to new life as the most prevalent RNA-binding protein involved in several neurological disorders, such as amyotrophic [...] Read more.
Transactive response DNA binding protein 43 kDa (TDP-43) was discovered in 2001 as a cellular factor capable to inhibit HIV-1 gene expression. Successively, it was brought to new life as the most prevalent RNA-binding protein involved in several neurological disorders, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the fact that these two research areas could be considered very distant from each other, in recent years an increasing number of publications pointed out the existence of a potentially important connection. Indeed, the ability of TDP-43 to act as an important regulator of all aspects of RNA metabolism makes this protein also a critical factor during expression of viral RNAs. Here, we summarize all recent observations regarding the involvement of TDP-43 in viral entry, replication and latency in several viruses that include enteroviruses (EVs), Theiler’s murine encephalomyelitis virus (TMEV), human immunodeficiency virus (HIV), human endogenous retroviruses (HERVs), hepatitis B virus (HBV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), West Nile virus (WNV), and herpes simplex virus-2 (HSV). In particular, in this work, we aimed to highlight the presence of similarities with the most commonly studied TDP-43 related neuronal dysfunctions. Full article
(This article belongs to the Special Issue RNA Metabolism: Role in Human Pathophysiology and Its Potential for Therapeutic Interventions)
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18 pages, 1765 KiB  
Review
Self-Amplifying RNA Approach for Protein Replacement Therapy
by Dimitri Papukashvili, Nino Rcheulishvili, Cong Liu, Yang Ji, Yunjiao He and Peng George Wang
Int. J. Mol. Sci. 2022, 23(21), 12884; https://doi.org/10.3390/ijms232112884 - 25 Oct 2022
Cited by 24 | Viewed by 6787
Abstract
Messenger RNA (mRNA) technology has already been successfully tested preclinically and there are ongoing clinical trials for protein replacement purposes; however, more effort has been put into the development of prevention strategies against infectious diseases. Apparently, mRNA vaccine approval against coronavirus disease 2019 [...] Read more.
Messenger RNA (mRNA) technology has already been successfully tested preclinically and there are ongoing clinical trials for protein replacement purposes; however, more effort has been put into the development of prevention strategies against infectious diseases. Apparently, mRNA vaccine approval against coronavirus disease 2019 (COVID-19) is a landmark for opening new opportunities for managing diverse health disorders based on this approach. Indeed, apart from infectious diseases, it has also been widely tested in numerous directions including cancer prevention and the treatment of inherited disorders. Interestingly, self-amplifying RNA (saRNA)-based technology is believed to display more developed RNA therapy compared with conventional mRNA technique in terms of its lower dosage requirements, relatively fewer side effects, and possessing long-lasting effects. Nevertheless, some challenges still exist that need to be overcome in order to achieve saRNA-based drug approval in clinics. Hence, the current review discusses the feasibility of saRNA utility for protein replacement therapy on various health disorders including rare hereditary diseases and also provides a detailed overview of saRNA advantages, its molecular structure, mechanism of action, and relevant delivery platforms. Full article
(This article belongs to the Special Issue RNA Metabolism: Role in Human Pathophysiology and Its Potential for Therapeutic Interventions)
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