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Genes
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Non-coding DNA in Human Health and Diseases
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Non-coding DNA in Human Health and Diseases

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 33539

Special Issue Editors

Dr. Isidoro Feliciello

E-Mail Website
Guest Editor
Department of Clinical Medicine and Surgery, University of Naples Federico II, 80100 Napoli, Italy
Interests: mobilome; satellite DNA; heterochromatin; evolution; gene regulation; satellite RNA; epigenetics; DNA repair
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Đurđica Ugarković

E-Mail Website
Guest Editor
Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia
Interests: satellite DNA; heterochromatin; evolution; gene regulation; satellite RNA; epigenetics

Special Issue Information

Dear Colleagues,

Coding DNA represents approximately 2% of the human genome, as well as of the genomes of other eukaryotic organisms. One of the most puzzling biological questions is understanding the purpose of the remaining 98% of the genome and how this non-coding DNA is linked to health. Genetic changes targeting non-coding DNA, such as substitution variants, duplications, insertions, deletions and translocations, can affect health and development. This Special Issue aims to identify regions of non-coding DNA, in particular those belonging to repetitive DNA, which play important role in cells and to understand how epigenetic and genetic changes of these regions affect their activity and in this way either influence certain genes, adaptation of the organisms as well as health conditions, or could serve as markers of specific pathological conditions.

Dr. Isidoro Feliciello
Prof. Dr. Đurđica Ugarković
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. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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

  • non-coding DNA
  • transposon
  • retrotransposon
  • satellite DNA
  • non-coding RNA
  • development
  • epigenetics
  • biomarker
  • disease
  • regulatory elements

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Published Papers (4 papers)

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Research

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21 pages, 2208 KiB  
Article
An Explanation of Exceptions from Chargaff’s Second Parity Rule/Strand Symmetry of DNA Molecules
by Marija Rosandić, Ines Vlahović, Ivan Pilaš, Matko Glunčić and Vladimir Paar
Genes 2022, 13(11), 1929; https://doi.org/10.3390/genes13111929 - 23 Oct 2022
Cited by 6 | Viewed by 2088
Abstract
In this article, we show that mono/oligonucleotide quadruplets, as basic structures of DNA, along with our classification of trinucleotides, disclose an organization of genomes based on purine–pyrimidine symmetry. Moreover, the structure and stability of DNA are influenced by the Watson–Crick pairing and the [...] Read more.
In this article, we show that mono/oligonucleotide quadruplets, as basic structures of DNA, along with our classification of trinucleotides, disclose an organization of genomes based on purine–pyrimidine symmetry. Moreover, the structure and stability of DNA are influenced by the Watson–Crick pairing and the natural law of DNA creation and conservation, according to which the same mono- or oligonucleotide insertion must be inserted simultaneously into both strands of DNA. Taken together, they lead to quadruplets with central mirror symmetry and bidirectional DNA strand orientation and are incorporated into Chargaff’s second parity rule (CSPR). Performing our quadruplet frequency analysis of all human chromosomes and of Neuroblastoma BreakPoint Family (NBPF) genes, which code Olduvai protein domains in the human genome, we show that the coding part of DNA violates CSPR. This may shed new light and give rise to a novel hypothesis on DNA creation and its evolution. In this framework, the logarithmic relationship between oligonucleotide order and minimal DNA sequence length, to establish the validity of CSPR, automatically follows from the quadruplet structure of the genomic sequence. The problem of the violation of CSPR in rare symbionts is discussed. Full article
(This article belongs to the Special Issue Non-coding DNA in Human Health and Diseases)
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12 pages, 926 KiB  
Article
Alpha Satellite RNA Levels Are Upregulated in the Blood of Patients with Metastatic Castration-Resistant Prostate Cancer
by Sven Ljubić, Antonio Sermek, Angela Prgomet Sečan, Marin Prpić, Blanka Jakšić, Jure Murgić, Ana Fröbe, Đurđica Ugarković and Isidoro Feliciello
Genes 2022, 13(2), 383; https://doi.org/10.3390/genes13020383 - 20 Feb 2022
Cited by 7 | Viewed by 3157
Abstract
The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we [...] Read more.
The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker. Full article
(This article belongs to the Special Issue Non-coding DNA in Human Health and Diseases)
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Review

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15 pages, 1014 KiB  
Review
Satellite DNAs in Health and Disease
by Đurđica Ugarković, Antonio Sermek, Sven Ljubić and Isidoro Feliciello
Genes 2022, 13(7), 1154; https://doi.org/10.3390/genes13071154 - 26 Jun 2022
Cited by 13 | Viewed by 3138
Abstract
Tandemly repeated satellite DNAs are major components of centromeres and pericentromeric heterochromatin which are crucial chromosomal elements responsible for accurate chromosome segregation. Satellite DNAs also contribute to genome evolution and the speciation process and are important for the maintenance of the entire genome [...] Read more.
Tandemly repeated satellite DNAs are major components of centromeres and pericentromeric heterochromatin which are crucial chromosomal elements responsible for accurate chromosome segregation. Satellite DNAs also contribute to genome evolution and the speciation process and are important for the maintenance of the entire genome inside the nucleus. In addition, there is increasing evidence for active and tightly regulated transcription of satellite DNAs and for the role of their transcripts in diverse processes. In this review, we focus on recent discoveries related to the regulation of satellite DNA expression and the role of their transcripts, either in heterochromatin establishment and centromere function or in gene expression regulation under various biological contexts. We discuss the role of satellite transcripts in the stress response and environmental adaptation as well as consequences of the dysregulation of satellite DNA expression in cancer and their potential use as cancer biomarkers. Full article
(This article belongs to the Special Issue Non-coding DNA in Human Health and Diseases)
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24 pages, 11966 KiB  
Review
mRNA Vaccines: Why Is the Biology of Retroposition Ignored?
by Tomislav Domazet-Lošo
Genes 2022, 13(5), 719; https://doi.org/10.3390/genes13050719 - 20 Apr 2022
Cited by 19 | Viewed by 23661
Abstract
The major advantage of mRNA vaccines over more conventional approaches is their potential for rapid development and large-scale deployment in pandemic situations. In the current COVID-19 crisis, two mRNA COVID-19 vaccines have been conditionally approved and broadly applied, while others are still in [...] Read more.
The major advantage of mRNA vaccines over more conventional approaches is their potential for rapid development and large-scale deployment in pandemic situations. In the current COVID-19 crisis, two mRNA COVID-19 vaccines have been conditionally approved and broadly applied, while others are still in clinical trials. However, there is no previous experience with the use of mRNA vaccines on a large scale in the general population. This warrants a careful evaluation of mRNA vaccine safety properties by considering all available knowledge about mRNA molecular biology and evolution. Here, I discuss the pervasive claim that mRNA-based vaccines cannot alter genomes. Surprisingly, this notion is widely stated in the mRNA vaccine literature but never supported by referencing any primary scientific papers that would specifically address this question. This discrepancy becomes even more puzzling if one considers previous work on the molecular and evolutionary aspects of retroposition in murine and human populations that clearly documents the frequent integration of mRNA molecules into genomes, including clinical contexts. By performing basic comparisons, I show that the sequence features of mRNA vaccines meet all known requirements for retroposition using L1 elements—the most abundant autonomously active retrotransposons in the human genome. In fact, many factors associated with mRNA vaccines increase the possibility of their L1-mediated retroposition. I conclude that is unfounded to a priori assume that mRNA-based therapeutics do not impact genomes and that the route to genome integration of vaccine mRNAs via endogenous L1 retroelements is easily conceivable. This implies that we urgently need experimental studies that would rigorously test for the potential retroposition of vaccine mRNAs. At present, the insertional mutagenesis safety of mRNA-based vaccines should be considered unresolved. Full article
(This article belongs to the Special Issue Non-coding DNA in Human Health and Diseases)
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