Recent Advances in RNA Editing and Modification

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

Deadline for manuscript submissions: 31 May 2025 | Viewed by 1373

Special Issue Editor


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Guest Editor
Japan Advanced Institute of Science and Technology, Area of Bioscience and Biotechnology, Nomi, Japan
Interests: RNA splicing; RNA editing; RNA modification; lncRNA; genetic code restoration
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Special Issue Information

Dear Colleagues,

RNA editing is the only physiological mechanism that alters the genetic code of DNA post-transcriptionally and is observed in a variety of species, from trypanosomes to mammals. RNA editing in mammals is A-to-I or C-to-U via the deamination of nucleobases, while U-to-C RNA editing via transamination is also present in plants.

Since genetic code conversion by RNA editing is sequence-specific and does not involve nucleotide strand breaks, it is expected to have fewer off-target effects than CRISPR-Cas systems. In addition, research on treating genetic diseases by artificial RNA editing has been active.

In 2011, Karijolich and Yu reported that pseudouridylation of the terminal codon U induces translational read-throughs. As mentioned previously, the I generated by the deamination of A is recognized as a G during translation because it forms a Watson–Crick base pair with C. These facts indicate that it is possible to transform genetic codes via base modification.

Furthermore, the m6A modification of mRNA, which is one of the most common modifications observed in mammals, has been shown to regulate various stages of mRNA, including maturation, nuclear export, translation, and degradation, and its regulation has been proposed for disease treatment. Thus, it is expected that new disease therapies will be developed through various RNA modifications in the future.

This Special Issue focuses on the latest developments in RNA editing and RNA modifications in plants and animals and welcomes advanced original research and review articles on the mechanisms, physiological roles, and applications, including disease treatments.

Prof. Dr. Toshifumi Tsukahara
Guest Editor

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Keywords

  • RNA editing
  • RNA modification
  • deamination
  • transamination
  • pseudouridylation

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Published Papers (2 papers)

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Research

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17 pages, 2054 KiB  
Article
Restoration of Genetic Code in Macular Mouse Fibroblasts via APOBEC1-Mediated RNA Editing
by Sonali Bhakta, Hiroko Kodama, Masakazu Mimaki and Toshifumi Tsukahara
Biomolecules 2025, 15(1), 136; https://doi.org/10.3390/biom15010136 - 16 Jan 2025
Viewed by 517
Abstract
RNA editing is a significant mechanism underlying genetic variation and protein molecule alteration; C-to-U RNA editing, specifically, is important in the regulation of mammalian genetic diversity. The ability to define and limit accesses of enzymatic machinery to avoid the modification of unintended targets [...] Read more.
RNA editing is a significant mechanism underlying genetic variation and protein molecule alteration; C-to-U RNA editing, specifically, is important in the regulation of mammalian genetic diversity. The ability to define and limit accesses of enzymatic machinery to avoid the modification of unintended targets is key to the success of RNA editing. Identification of the core component of the apoB RNA editing holoenzyme, APOBEC, and investigation into new candidate genes encoding other elements of the complex could reveal further details regarding APOBEC-mediated mRNA editing. Menkes disease is a recessive X-chromosome-linked hereditary syndrome in humans, caused by defective copper metabolism due to mutations in the ATP7A gene, which encodes a copper transport protein. Here, we generated plasmids encoding the MS2 system and the APOBEC1 deaminase domain and used a guide RNA with flanking MS2 sites to restore mutated Atp7a in fibroblasts from a macular mouse model of Menkes disease withs T>C mutation. Around 35% of the mutated C nucleotide (nt) was restored to U, demonstrating that our RNA editing system is reliable and has potential for therapeutic clinical application. RNA base editing via human RNA-guided cytidine deaminases is a potentially attractive approach for in vivo therapeutic application and provides opportunities for new developments in this field. Full article
(This article belongs to the Special Issue Recent Advances in RNA Editing and Modification)
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Review

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17 pages, 1794 KiB  
Review
Heavy Chalcogen Properties of Sulfur and Selenium Enhance Nucleic Acid-Based Therapeutics
by Stephen J. Dansereau and Jia Sheng
Biomolecules 2025, 15(2), 218; https://doi.org/10.3390/biom15020218 - 2 Feb 2025
Viewed by 539
Abstract
The Group 16 elements of the periodic table have a characteristic valence shell configuration instrumental to their chemical properties and reactivities. The electrostatic potentials of these so-called chalcogens have been exploited in the design of materials that require the efficient passage of electrons [...] Read more.
The Group 16 elements of the periodic table have a characteristic valence shell configuration instrumental to their chemical properties and reactivities. The electrostatic potentials of these so-called chalcogens have been exploited in the design of materials that require the efficient passage of electrons including supermagnets, photocatalytic dyes, and solar panels. Likewise, the incorporation of the heavy chalcogen selenium into organic frameworks has been shown to increase the reactivities of double bonds and heterocyclic rings, while its interactions with aromatic side chains in the hydrophobic core of proteins such as selenomethionine impart a stabilizing effect. Typically present in the active site, the hypervalence of selenocysteine enables it to further stabilize the folded protein and mediate electron transfer. Selenium’s native occurrence in bacterial tRNA maintains base pair fidelity, most notably during oxidative stress, through its electronic and steric effects. Such native modifications at the position 2 and 5 of uridine render these sites relevant in the design of RNA-based therapeutics. Innocuous selenium substitution for oxygen in the former and the standard methods of selenium-derivatized oligonucleotide synthesis and detection have led to the establishment of a novel class of therapeutics. In this review, we summarize some progress in this area. Full article
(This article belongs to the Special Issue Recent Advances in RNA Editing and Modification)
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