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RNA Modification
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RNA Modification

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

Deadline for manuscript submissions: closed (15 September 2017) | Viewed by 32450

Special Issue Editor

Dr. Kumiko Ui-Tei

E-Mail Website
Guest Editor
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan
Interests: gene regulation; protein-noncoding RNAs; short interfering RNAs; microRNAs

Special Issue Information

Dear Colleagues,

RNA modification is revealed to be an additional regulatory layer of the primary transcriptome. The major RNA modifications in the eukaryotic cells are N6-methyladenosine (m6A), 5-methylcytidine (m5C), N1-methyladenosine (m1A), inosine or pseudouridine. These modifications regulate various kinds of important physiological processes involving stress and immune responses, or epigenetic inheritance by regulating gene expression at multiple steps. They are known to be enriched in tRNAs, but recent improvement of sequence technology revealed that RNA modifications are also observed in other RNA molecules involving small RNAs or long non-coding RNAs. Thus, RNA modifications play important roles in eukaryotic genome recoding processes during environmental responses or diseases. In this Special Issue, we welcome submissions of original articles as well as reviews of any topics related to RNA modifications for a better understanding on new perspectives and interpretations as well as novel technological and theoretical progresses.

Dr. Kumiko UI-TEI
Guest Editor

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

  • RNA modification
  • RNA editing
  • RNA methylation
  • gene expression regulation
  • non-coding RNA
  • small RNA
  • genome recoding

Published Papers (6 papers)

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Research

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979 KiB  
Article
5-Fluorouracil Treatment Alters the Efficiency of Translational Recoding
by Junhui Ge, John Karijolich, Yingzhen Zhai, Jianming Zheng and Yi-Tao Yu
Genes 2017, 8(11), 295; https://doi.org/10.3390/genes8110295 - 31 Oct 2017
Cited by 7 | Viewed by 3679
Abstract
5-fluorouracil (5-FU) is a chemotherapeutic agent that has been extensively studied since its initial development in the 1950s. It has been suggested that the mechanism of action of 5-FU involves both DNA- and RNA-directed processes, but this has remained controversial. In this study, [...] Read more.
5-fluorouracil (5-FU) is a chemotherapeutic agent that has been extensively studied since its initial development in the 1950s. It has been suggested that the mechanism of action of 5-FU involves both DNA- and RNA-directed processes, but this has remained controversial. In this study, using a series of in vivo reporter constructs capable of measuring translational recoding, we demonstrate that cells exposed to 5-FU display a reduced capacity to engage in a variety of translational recoding events, including +1 programmed frameshifting (PRF) and −1 PRF. In addition, 5-FU-treated cells are much less accurate at stop codon recognition, resulting in a significant increase in stop codon-readthrough. Remarkably, while the efficiency of cap-dependent translation appears to be unaffected by 5-FU, 5-FU-treated cells display a decreased ability to initiate cap-independent translation. We further show that knockdown of thymidylate synthase, an enzyme believed to be at the center of 5-FU-induced DNA damage, has no effect on the observed alterations in translational recoding. On the other hand, ribosomal RNA (rRNA) pseudouridylation, which plays an important role in translational recoding, is significantly inhibited. Taken together, our results suggest that the observed effect of 5-FU on recoding is an RNA-directed effect. Our results are the first to show definitely and quantitatively that translational recoding is affected by exposure to 5-FU. Thus, it is possible that a substantial portion of 5-FU cytotoxicity might possibly be the result of alterations in translational recoding efficiency. Full article
(This article belongs to the Special Issue RNA Modification)
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1033 KiB  
Article
Quantification of Pseudouridine Levels in Cellular RNA Pools with a Modified HPLC-UV Assay
by Jialin Xu, Alice Y. Gu, Naresh R. Thumati and Judy M.Y. Wong
Genes 2017, 8(9), 219; https://doi.org/10.3390/genes8090219 - 05 Sep 2017
Cited by 5 | Viewed by 5037
Abstract
Pseudouridine (Ψ) is the most abundant post-transcriptionally modified ribonucleoside. Different Ψ modifications correlate with stress responses and are postulated to coordinate the distinct biological responses to a diverse panel of cellular stresses. With the help of different guide RNAs, the dyskerin complex pseudouridylates [...] Read more.
Pseudouridine (Ψ) is the most abundant post-transcriptionally modified ribonucleoside. Different Ψ modifications correlate with stress responses and are postulated to coordinate the distinct biological responses to a diverse panel of cellular stresses. With the help of different guide RNAs, the dyskerin complex pseudouridylates ribosomal RNA, small nuclear RNA and selective messenger RNAs. To monitor Ψ levels quantitatively, a previously reported high performance liquid chromatography method coupled with ultraviolet detection (HPLC-UV) was modified to determine total Ψ levels in different cellular RNA fractions. Our method was validated to be accurate and precise within the linear range of 0.06–15.36 pmol/μL and to have absolute Ψ quantification levels as low as 3.07 pmol. Using our optimized HPLC assay, we found that 1.20% and 1.94% of all ribonucleosides in nuclear-enriched RNA and small non-coding RNA pools from the HEK293 cell line, and 1.77% and 0.98% of ribonucleosides in 18S and 28S rRNA isolated from the HeLa cell line, were pseudouridylated. Upon knockdown of dyskerin expression, a consistent and significant reduction in total Ψ levels in nuclear-enriched RNA pools was observed. Our assay provides a fast and accurate quantification method to measure changes in Ψ levels of different RNA pools without sample derivatization. Full article
(This article belongs to the Special Issue RNA Modification)
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2998 KiB  
Article
Analysis of Argonaute 4-Associated Long Non-Coding RNA in Arabidopsis thaliana Sheds Novel Insights into Gene Regulation through RNA-Directed DNA Methylation
by Phil Chi Khang Au, Elizabeth S. Dennis and Ming-Bo Wang
Genes 2017, 8(8), 198; https://doi.org/10.3390/genes8080198 - 07 Aug 2017
Cited by 19 | Viewed by 6659
Abstract
RNA-directed DNA methylation (RdDM) is a plant-specific de novo DNA methylation mechanism that requires long noncoding RNA (lncRNA) as scaffold to define target genomic loci. While the role of RdDM in maintaining genome stability is well established, how it regulates protein-coding genes remains [...] Read more.
RNA-directed DNA methylation (RdDM) is a plant-specific de novo DNA methylation mechanism that requires long noncoding RNA (lncRNA) as scaffold to define target genomic loci. While the role of RdDM in maintaining genome stability is well established, how it regulates protein-coding genes remains poorly understood and few RdDM target genes have been identified. In this study, we obtained sequences of RdDM-associated lncRNAs using nuclear RNA immunoprecipitation against ARGONAUTE 4 (AGO4), a key component of RdDM that binds specifically with the lncRNA. Comparison of these lncRNAs with gene expression data of RdDM mutants identified novel RdDM target genes. Surprisingly, a large proportion of these target genes were repressed in RdDM mutants suggesting that they are normally activated by RdDM. These RdDM-activated genes are more enriched for gene body lncRNA than the RdDM-repressed genes. Histone modification and RNA analyses of several RdDM-activated stress response genes detected increased levels of active histone mark and short RNA transcript in the lncRNA-overlapping gene body regions in the ago4 mutant despite the repressed expression of these genes. These results suggest that RdDM, or AGO4, may play a role in maintaining or activating stress response gene expression by directing gene body chromatin modification preventing cryptic transcription. Full article
(This article belongs to the Special Issue RNA Modification)
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Review

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607 KiB  
Review
Role of Non-Coding RNAs in the Etiology of Bladder Cancer
by Caterina Gulìa, Stefano Baldassarra, Fabrizio Signore, Giuliano Rigon, Valerio Pizzuti, Marco Gaffi, Vito Briganti, Alessandro Porrello and Roberto Piergentili
Genes 2017, 8(11), 339; https://doi.org/10.3390/genes8110339 - 22 Nov 2017
Cited by 37 | Viewed by 4497
Abstract
According to data of the International Agency for Research on Cancer and the World Health Organization (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organization Mortality), bladder is among the top ten body locations of cancer globally, with the highest incidence [...] Read more.
According to data of the International Agency for Research on Cancer and the World Health Organization (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organization Mortality), bladder is among the top ten body locations of cancer globally, with the highest incidence rates reported in Southern and Western Europe, North America, Northern Africa and Western Asia. Males (M) are more vulnerable to this disease than females (F), despite ample frequency variations in different countries, with a M:F ratio of 4.1:1 for incidence and 3.6:1 for mortality, worldwide. For a long time, bladder cancer was genetically classified through mutations of two genes, fibroblast growth factor receptor 3 (FGFR3, for low-grade, non-invasive papillary tumors) and tumor protein P53 (TP53, for high-grade, muscle-invasive tumors). However, more recently scientists have shown that this disease is far more complex, since genes directly involved are more than 150; so far, it has been described that altered gene expression (up- or down-regulation) may be present for up to 500 coding sequences in low-grade and up to 2300 in high-grade tumors. Non-coding RNAs are essential to explain, at least partially, this ample dysregulation. In this review, we summarize the present knowledge about long and short non-coding RNAs that have been linked to bladder cancer etiology. Full article
(This article belongs to the Special Issue RNA Modification)
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607 KiB  
Review
RNA Pseudouridylation in Physiology and Medicine: For Better and for Worse
by Marianna Penzo, Ania N. Guerrieri, Federico Zacchini, Davide Treré and Lorenzo Montanaro
Genes 2017, 8(11), 301; https://doi.org/10.3390/genes8110301 - 01 Nov 2017
Cited by 64 | Viewed by 6500
Abstract
Pseudouridine is the most abundant modification found in RNA. Today, thanks to next-generation sequencing techniques used in the detection of RNA modifications, pseudouridylation sites have been described in most eukaryotic RNA classes. In the present review, we will first consider the available information [...] Read more.
Pseudouridine is the most abundant modification found in RNA. Today, thanks to next-generation sequencing techniques used in the detection of RNA modifications, pseudouridylation sites have been described in most eukaryotic RNA classes. In the present review, we will first consider the available information on the functional roles of pseudouridine(s) in different RNA species. We will then focus on how alterations in the pseudouridylation process may be connected with a series of human pathologies, including inherited disorders, cancer, diabetes, and viral infections. Finally, we will discuss how the availability of novel technical approaches are likely to increase the knowledge in this field. Full article
(This article belongs to the Special Issue RNA Modification)
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315 KiB  
Review
Extracellular Vesicle‐Associated RNA as a Carrier of Epigenetic Information
by Carlo Maria Di Liegro, Gabriella Schiera and Italia Di Liegro
Genes 2017, 8(10), 240; https://doi.org/10.3390/genes8100240 - 22 Sep 2017
Cited by 39 | Viewed by 5504
Abstract
Post‐transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis‐acting signals (zip codes), usually present in their 5′‐ and 3′‐untranslated regions (UTRs). By binding [...] Read more.
Post‐transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis‐acting signals (zip codes), usually present in their 5′‐ and 3′‐untranslated regions (UTRs). By binding to these signals, trans‐acting factors, such as RNA‐binding proteins (RBPs), and/or non‐coding RNAs (ncRNAs), control mRNA localization, translation and stability. RBPs can also form complexes with non‐coding RNAs of different sizes. The release of extracellular vesicles (EVs) is a conserved process that allows both normal and cancer cells to horizontally transfer molecules, and hence properties, to neighboring cells. By interacting with proteins that are specifically sorted to EVs, mRNAs as well as ncRNAs can be transferred from cell to cell. In this review, we discuss the mechanisms underlying the sorting to EVs of different classes of molecules, as well as the role of extracellular RNAs and the associated proteins in altering gene expression in the recipient cells. Importantly, if, on the one hand, RBPs play a critical role in transferring RNAs through EVs, RNA itself could, on the other hand, function as a carrier to transfer proteins (i.e., chromatin modifiers, and transcription factors) that, once transferred, can alter the cell’s epigenome. Full article
(This article belongs to the Special Issue RNA Modification)
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