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Correction: Tusup et al. Evaluation of the Interplay between the ADAR Editome and Immunotherapy in Melanoma. Non-Coding RNA 2021, 7, 5

by Marina Tusup, Phil F. Cheng, Ernesto Picardi, Austeja Raziunaite, Reinhard Dummer, Mitchell P. Levesque, Lars E. French, Emmanuella Guenova, Thomas M. Kundig and Steve Pascolo

Non-Coding RNA 2022, 8(6), 79; https://doi.org/10.3390/ncrna8060079 - 21 Nov 2022

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Abstract

In the original article [...] Full article

(This article belongs to the Section RNA Modifications)

14 pages, 1839 KiB

Open AccessArticle

Staphylococcus aureus Small RNAs Possess Dephospho-CoA 5′-Caps, but No CoAlation Marks

by Christian Löcherer, Nadja Bühler, Pascal Lafrenz and Andres Jäschke

Non-Coding RNA 2022, 8(4), 46; https://doi.org/10.3390/ncrna8040046 - 28 Jun 2022

Cited by 4 | Viewed by 3429

Abstract

Novel features of coenzyme A (CoA) and its precursor, 3′-dephospho-CoA (dpCoA), recently became evident. dpCoA was found to attach to 5′-ends of small ribonucleic acids (dpCoA-RNAs) in two bacterial species (Escherichia coli and Streptomyces venezuelae). Furthermore, CoA serves, in addition to its well-established coenzymatic roles, as a ubiquitous posttranslational protein modification (‘CoAlation’), thought to prevent the irreversible oxidation of cysteines. Here, we first identified and quantified dpCoA-RNAs in the small RNA fraction of the human pathogen Staphylococcus aureus, using a newly developed enzymatic assay. We found that the amount of dpCoA caps was similar to that of the other two bacteria. We furthermore tested the hypothesis that, in the environment of a cell, the free thiol of the dpCoA-RNAs, as well as other sulfur-containing RNA modifications, may be oxidized by disulfide bond formation, e.g., with CoA. While we could not find evidence for such an ‘RNA CoAlation’, we observed that CoA disulfide reductase, the enzyme responsible for reducing CoA homodisulfides in S. aureus, did efficiently reduce several synthetic dpCoA-RNA disulfides to dpCoA-RNAs in vitro. This activity may imply a role in reversing RNA CoAlation. Full article

(This article belongs to the Collection Research on RNA Modification)

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19 pages, 1624 KiB

Open AccessReview

The Importance of the Epi-Transcriptome in Translation Fidelity

by Charlène Valadon and Olivier Namy

Non-Coding RNA 2021, 7(3), 51; https://doi.org/10.3390/ncrna7030051 - 27 Aug 2021

Cited by 11 | Viewed by 5530

Abstract

RNA modifications play an essential role in determining RNA fate. Recent studies have revealed the effects of such modifications on all steps of RNA metabolism. These modifications range from the addition of simple groups, such as methyl groups, to the addition of highly complex structures, such as sugars. Their consequences for translation fidelity are not always well documented. Unlike the well-known m⁶A modification, they are thought to have direct effects on either the folding of the molecule or the ability of tRNAs to bind their codons. Here we describe how modifications found in tRNAs anticodon-loop, rRNA, and mRNA can affect translation fidelity, and how approaches based on direct manipulations of the level of RNA modification could potentially be used to modulate translation for the treatment of human genetic diseases. Full article

(This article belongs to the Collection Research on RNA Modification)

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15 pages, 8026 KiB

Open AccessArticle

Changes of the tRNA Modification Pattern during the Development of Dictyostelium discoideum

by Anne Hoffmann, Lieselotte Erber, Heike Betat, Peter F. Stadler, Mario Mörl and Jörg Fallmann

Non-Coding RNA 2021, 7(2), 32; https://doi.org/10.3390/ncrna7020032 - 28 May 2021

Cited by 2 | Viewed by 5591

Abstract

Dictyostelium discoideum is a social amoeba, which on starvation develops from a single-cell state to a multicellular fruiting body. This developmental process is accompanied by massive changes in gene expression, which also affect non-coding RNAs. Here, we investigate how tRNAs as key regulators of the translation process are affected by this transition. To this end, we used LOTTE-seq to sequence the tRNA pool of D. discoideum at different developmental time points and analyzed both tRNA composition and tRNA modification patterns. We developed a workflow for the specific detection of modifications from reverse transcriptase signatures in chemically untreated RNA-seq data at single-nucleotide resolution. It avoids the comparison of treated and untreated RNA-seq data using reverse transcription arrest patterns at nucleotides in the neighborhood of a putative modification site as internal control. We find that nucleotide modification sites in D. discoideum tRNAs largely conform to the modification patterns observed throughout the eukaroytes. However, there are also previously undescribed modification sites. We observe substantial dynamic changes of both expression levels and modification patterns of certain tRNA types during fruiting body development. Beyond the specific application to D. discoideum our results demonstrate that the developmental variability of tRNA expression and modification can be traced efficiently with LOTTE-seq. Full article

(This article belongs to the Collection Research on RNA Modification)

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11 pages, 1995 KiB

Open AccessArticle

Evaluation of the Interplay between the ADAR Editome and Immunotherapy in Melanoma

Non-Coding RNA 2021, 7(1), 5; https://doi.org/10.3390/ncrna7010005 - 12 Jan 2021

Cited by 4 | Viewed by 4951 | Correction

Abstract

Background: RNA editing is a highly conserved posttranscriptional mechanism that contributes to transcriptome diversity. In mammals, it includes nucleobase deaminations that convert cytidine (C) into uridine (U) and adenosine (A) into inosine (I). Evidence from cancer studies indicates that RNA-editing enzymes promote certain mechanisms of tumorigenesis. On the other hand, recoding editing in mRNA can generate mutations in proteins that can participate in the Major Histocompatibility Complex (MHC) ligandome and can therefore be recognized by the adaptive immune system. Anti-cancer treatment based on the administration of immune checkpoint inhibitors enhance these natural anti-cancer immune responses. Results: Based on RNA-Seq datasets, we evaluated the editome of melanoma cell lines generated from patients pre- and post-immunotherapy with immune checkpoint inhibitors. Our results reveal a differential editing in Arthrobacter luteus (Alu) sequences between samples pre-therapy and relapses during therapy with immune checkpoint inhibitors. Conclusion: These data pave the way towards the development of new diagnostics and therapies targeted to editing that could help in preventing relapses during immunotherapies. Full article

(This article belongs to the Collection Research on RNA Modification)

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