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RNA in Biology and Medicine
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RNA in Biology and Medicine

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: 20 December 2024 | Viewed by 5352

Special Issue Editors

Dr. Roberto Patarca

E-Mail Website
Guest Editor
Roberto Patarca (Author), Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY 11030, USA
Interests: bioinformatics insights on viral gene expression transactivation: from HIV-1 to SARS-CoV-2
Dr. William A. Haseltine

E-Mail Website
Guest Editor
1. ACCESS Health International, 384 West Lane, Ridgefield, CT 06877, USA
2. Regenerative Medicine Program, Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY 11030, USA
Interests: regenerative medicine; molecular medicine; virology; genomics; public health

Special Issue Information

Dear Colleagues,

The advent of messenger RNA vaccines against the severe acute respiratory syndrome coronavirus-2 and certain forms of cancer and studies on noncoding RNAs have ushered in an era of medical uses of RNA. This revolution has been heralded by the realization that RNA plays a more fundamental role than that reflected in the classical central molecular biology dogma, in which genetic information flows from DNA to RNA to protein to phenotype. In the new dogma, RNA directly or indirectly determines phenotype by regulating protein function and not just driving protein expression.

The importance of noncoding RNAs is underscored by the fact that approximately 97% of the transcriptional output of the human genome is generated by non-protein-coding RNA genes. The RNAs encoded by these genes and, in some cases, by protein-coding RNA genes interact with various molecules to regulate processes such as gene expression regulation, chromatin remodeling, epigenetic modifications, and cellular growth, proliferation, and survival.

The Special Issue aims to provide a much-needed overview of the status and future trends of knowledge on RNAs from primary to tertiary structure and function to clinical applications of RNA-based technologies in vaccinology, chimeric antigen receptor (CAR) T cells, immunoregulation, and gene therapy, among others. We welcome contributions, including original research articles, reviews, and perspectives, on the vast family of RNAs, from viroids and virusoids to cellular coding and noncoding RNAs.

Dr. Roberto Patarca
Dr. William A. Haseltine
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

  • noncoding RNAs
  • coding RNAs
  • RNA-based therapy
  • RNA vaccine
  • RNA structure
  • RNA function

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Published Papers (4 papers)

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Research

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23 pages, 3752 KiB  
Article
Differentiation and Growth-Arrest-Related lncRNA (DAGAR): Initial Characterization in Human Smooth Muscle and Fibroblast Cells
by Benjamin de la Cruz-Thea, Lautaro Natali, Hung Ho-Xuan, Astrid Bruckmann, Núria Coll-Bonfill, Nicholas Strieder, Víctor I. Peinado, Gunter Meister and Melina M. Musri
Int. J. Mol. Sci. 2024, 25(17), 9497; https://doi.org/10.3390/ijms25179497 - 31 Aug 2024
Viewed by 1228
Abstract
Vascular smooth muscle cells (SMCs) can transition between a quiescent contractile or “differentiated” phenotype and a “proliferative-dedifferentiated” phenotype in response to environmental cues, similar to what in occurs in the wound healing process observed in fibroblasts. When dysregulated, these processes contribute to the [...] Read more.
Vascular smooth muscle cells (SMCs) can transition between a quiescent contractile or “differentiated” phenotype and a “proliferative-dedifferentiated” phenotype in response to environmental cues, similar to what in occurs in the wound healing process observed in fibroblasts. When dysregulated, these processes contribute to the development of various lung and cardiovascular diseases such as Chronic Obstructive Pulmonary Disease (COPD). Long non-coding RNAs (lncRNAs) have emerged as key modulators of SMC differentiation and phenotypic changes. In this study, we examined the expression of lncRNAs in primary human pulmonary artery SMCs (hPASMCs) during cell-to-cell contact-induced SMC differentiation. We discovered a novel lncRNA, which we named Differentiation And Growth Arrest-Related lncRNA (DAGAR) that was significantly upregulated in the quiescent phenotype with respect to proliferative SMCs and in cell-cycle-arrested MRC5 lung fibroblasts. We demonstrated that DAGAR expression is essential for SMC quiescence and its knockdown hinders SMC differentiation. The treatment of quiescent SMCs with the pro-inflammatory cytokine Tumor Necrosis Factor (TNF), a known inducer of SMC dedifferentiation and proliferation, elicited DAGAR downregulation. Consistent with this, we observed diminished DAGAR expression in pulmonary arteries from COPD patients compared to non-smoker controls. Through pulldown experiments followed by mass spectrometry analysis, we identified several proteins that interact with DAGAR that are related to cell differentiation, the cell cycle, cytoskeleton organization, iron metabolism, and the N-6-Methyladenosine (m6A) machinery. In conclusion, our findings highlight DAGAR as a novel lncRNA that plays a crucial role in the regulation of cell proliferation and SMC differentiation. This paper underscores the potential significance of DAGAR in SMC and fibroblast physiology in health and disease. Full article
(This article belongs to the Special Issue RNA in Biology and Medicine)
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28 pages, 7550 KiB  
Article
Potential Transcriptional Enhancers in Coronaviruses: From Infectious Bronchitis Virus to SARS-CoV-2
by Roberto Patarca and William A. Haseltine
Int. J. Mol. Sci. 2024, 25(15), 8012; https://doi.org/10.3390/ijms25158012 - 23 Jul 2024
Viewed by 960
Abstract
Coronaviruses constitute a global threat to human and animal health. It is essential to investigate the long-distance RNA-RNA interactions that approximate remote regulatory elements in strategies, including genome circularization, discontinuous transcription, and transcriptional enhancers, aimed at the rapid replication of their large genomes, [...] Read more.
Coronaviruses constitute a global threat to human and animal health. It is essential to investigate the long-distance RNA-RNA interactions that approximate remote regulatory elements in strategies, including genome circularization, discontinuous transcription, and transcriptional enhancers, aimed at the rapid replication of their large genomes, pathogenicity, and immune evasion. Based on the primary sequences and modeled RNA-RNA interactions of two experimentally defined coronaviral enhancers, we detected via an in silico primary and secondary structural analysis potential enhancers in various coronaviruses, from the phylogenetically ancient avian infectious bronchitis virus (IBV) to the recently emerged SARS-CoV-2. These potential enhancers possess a core duplex-forming region that could transition between closed and open states, as molecular switches directed by viral or host factors. The duplex open state would pair with remote sequences in the viral genome and modulate the expression of downstream crucial genes involved in viral replication and host immune evasion. Consistently, variations in the predicted IBV enhancer region or its distant targets coincide with cases of viral attenuation, possibly driven by decreased open reading frame (ORF)3a immune evasion protein expression. If validated experimentally, the annotated enhancer sequences could inform structural prediction tools and antiviral interventions. Full article
(This article belongs to the Special Issue RNA in Biology and Medicine)
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Review

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22 pages, 3332 KiB  
Review
MicroRNAs in Lung Cancer Brain Metastasis
by Israel Martínez-Espinosa, José A. Serrato and Blanca Ortiz-Quintero
Int. J. Mol. Sci. 2024, 25(19), 10325; https://doi.org/10.3390/ijms251910325 - 25 Sep 2024
Viewed by 1228
Abstract
Brain metastasis is a significant clinical challenge for patients with advanced lung cancer, occurring in about 20–40% of cases. Brain metastasis causes severe neurological symptoms, leading to a poor prognosis and contributing significantly to lung cancer-related mortality. However, the underlying molecular mechanism behind [...] Read more.
Brain metastasis is a significant clinical challenge for patients with advanced lung cancer, occurring in about 20–40% of cases. Brain metastasis causes severe neurological symptoms, leading to a poor prognosis and contributing significantly to lung cancer-related mortality. However, the underlying molecular mechanism behind brain metastasis remains largely unknown. MicroRNAs (miRNAs) are small, non-coding RNAs linked to several aspects of cancer progression, including metastasis. In the context of lung cancer, significant research has shown the involvement of miRNAs in regulating critical pathways related to metastatic spread to the brain. This review summarizes the scientific evidence regarding the regulatory roles of intra- and extracellular miRNAs, which specifically drive the spread of lung cancer cells to the brain. It also revises the known molecular mechanisms of brain metastasis, focusing on those from lung cancer as the primary tumor to better understand the complex mechanisms underlying this regulation. Understanding these complex regulatory mechanisms holds promise for developing novel diagnostic biomarkers and potential therapeutic strategies in brain metastasis. Full article
(This article belongs to the Special Issue RNA in Biology and Medicine)
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20 pages, 885 KiB  
Review
Long Non-Coding RNAs in Neuroblastoma: Pathogenesis, Biomarkers and Therapeutic Targets
by Niels Vercouillie, Zhiyao Ren, Eva Terras and Tim Lammens
Int. J. Mol. Sci. 2024, 25(11), 5690; https://doi.org/10.3390/ijms25115690 - 23 May 2024
Viewed by 1339
Abstract
Neuroblastoma is the most common malignant extracranial solid tumor of childhood. Recent studies involving the application of advanced high-throughput “omics” techniques have revealed numerous genomic alterations, including aberrant coding-gene transcript levels and dysfunctional pathways, that drive the onset, growth, progression, and treatment resistance [...] Read more.
Neuroblastoma is the most common malignant extracranial solid tumor of childhood. Recent studies involving the application of advanced high-throughput “omics” techniques have revealed numerous genomic alterations, including aberrant coding-gene transcript levels and dysfunctional pathways, that drive the onset, growth, progression, and treatment resistance of neuroblastoma. Research conducted in the past decade has shown that long non-coding RNAs, once thought to be transcriptomic noise, play key roles in cancer development. With the recent and continuing increase in the amount of evidence for the underlying roles of long non-coding RNAs in neuroblastoma, the potential clinical implications of these RNAs cannot be ignored. In this review, we discuss their biological mechanisms of action in the context of the central driving mechanisms of neuroblastoma, focusing on potential contributions to the diagnosis, prognosis, and treatment of this disease. We also aim to provide a clear, integrated picture of future research opportunities. Full article
(This article belongs to the Special Issue RNA in Biology and Medicine)
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