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At least 19 recordsLinked to original sources

PubMed2024

TGIRT-seq to profile tRNA-derived RNAs and associated RNA modifications.

RNA modifications are key regulators for RNA processes. tRNA-derived RNAs are small RNAs with size between 15 and 50 bases long that are processed from mature or precursor tRNAs. Despite their more recent discovery, tRNA-derived RNAs have been found to play regulatory roles in many cellular processes including gene silencing, protein synthesis, stress response, and transgenerational inheritance. Furthermore, tRNA-derived RNAs are highly abundant in bodily fluids, posing as potential biomarkers. A unique feature of tRNA-derived RNAs is that they are rich in RNA modifications. Many of the RNA modifications on tRNA-derived RNAs disrupt Watson-Crick base pairing and will thus stall reverse transcriptase, such as N1-methyladenosine (m1A), N1-methylguanosine (m1G) and N2, N2-dimethylguanosine (m22G). These RNA modifications add another layer of regulation onto tRNA-derived RNAs' functions and are of interests for future research. However, these RNA modifications could also lead to lower detection of modification-containing RNAs in genome-wide small RNA sequencing analysis due to reverse transcriptase stall. To circumvent this bias, TGIRT (Thermostable Group II Intron Reverse Transcriptase) has been used to readthrough RNA modifications inserting mismatches. These mismatch signatures can then be used to precisely map the modification sites at base resolution. Here we describe the step-by-step experimental protocol to start with purified RNAs from cells or tissues and use TGIRT to make small RNA sequencing library for Illumina sequencing to profile the abundance of tRNA-derived RNAs and the associated RNA modifications.

RNA, Transfer↗

PubMed2026

DirectASRM: uncovering allele-specific post-transcriptional RNA modifications through direct RNA sequencing.

SUMMARY: We developed DirectASRM, a comprehensive database for the systematic identification, integration, and annotation of allele-specific RNA modifications (ASRMs) from direct RNA sequencing data. DirectASRM enables single-base, transcript-level detection of ASRMs across multiple RNA modification types, diverse organisms and condition-specific contexts. The database further evaluates the confidence of each ASRM-SNP pair association within isoform context by jointly considering statistical evidence of allelic modification imbalance and independent support from external next-generation sequencing (NGS) - based RNA modification resources. DirectASRM also provides extensive functional annotations for ASRMs and their associated variants, including intra-sample transcript-level allele-specific expression (ASE) and allele-specific splicing, as well as additional post-transcriptional regulatory features such as miRNA binding, circRNA, RNA-protein interactions, and disease relevance. Overall, DirectASRM serves as a comprehensive resource that supports systematic investigation of the potential functional impact of genetic variants in epitranscriptomic regulation. AVAILABILITY AND IMPLEMENTATION: DirectASRM database is freely accessible at http://modinfor.com/DirectASRM/. DirectASRM pipeline is available at GitHub (https://github.com/jiayin1101/DirectASRM_pipeline) and Zenodo (DOI: https://doi.org/10.5281/zenodo.19876077).

Alleles↗

PubMed2026

DREAMS illuminates spatial DNA and RNA modification landscapes.

DNA and RNA modifications regulate gene expression and RNA processing, but their spatial organization in complex tissues remains elusive. Here we developed DNA RNA Elements Areal Mass Spectrometry (DREAMS), a mass spectrometry imaging platform that spatially maps diverse nucleic acid modifications simultaneously. Applying DREAMS to TET-deficient mouse brains (Tet1Δ/Δ and triple Tet1/2/3Δ/Δ), we uncover TET1's unexpected role in modulating N1-methyladenosine (m1A), a pivotal RNA modification. While DREAMS reveals broad modification landscapes altered across TET knockouts, we identify TET1-mediated changes in m1A that correlate with transcriptome alterations. Our work establishes DREAMS as a transformative tool for spatial epigenomics/epitranscriptomics and suggests that TET enzymes could influence multiple DNA and RNA modifications with potential gatekeeping roles in nucleic acid regulation.

Animals↗

PubMed1996

The RNA modification database.

The RNA modification database provides a comprehensive listing of post-transcriptionally modified nucleosides from RNA and is maintained as an updated version of the initial printed report. Information provided includes: type(s) of RNA in which found and phylogenetic distribution; common chemical names and symbols; Chemical Abstracts registry numbers and index names; chemical structures; initial literature citations for structural characterization or occurrence and chemical synthesis. The data are available through the World Wide Web, anonymous ftp or from the authors in printed form.

Computer Communication Networks↗

PubMed2026

Quantitative RNA modification mapping by mass spectrometry with isobaric tags and nucleobase fragment analysis.

RNA modifications regulate RNA stability, translation, stress responses, and disease processes, yet their function remains poorly understood due to technical limitations in sequence analysis. Here, we present an RNA-specific isobaric tandem mass tagging (RMT) platform for omic-scale quantitative mapping of RNA modifications. The platform combines RNA-specific tags adapted from proteomics with an end-to-end workflow spanning sample preparation through data processing. Validation using synthetic oligonucleotides and total tRNA from Pseudomonas aeruginosa yielded reproducible quantification, with coefficients of variation below 5%. Together with nucleobase fragment analysis, we identified and quantified 24 RNA modifications in PA14 tRNAs, including previously undescribed m2A38 and Gm/Cm39, and assigned their corresponding writer enzymes. Further analyses of tRNAs from writer knockout strains and stressed cells revealed dynamic modification patterns, modification interdependencies, and their potential roles in stress adaptation. This method provides a robust, cost-effective platform for quantitative RNA modification mapping, enabling deeper biological insights.

RNA, Transfer↗

PubMed1997

The RNA modification database.

The RNA modification database provides a comprehensive listing of posttranscriptionally modified nucleosides from all RNAs, and is maintained as an updated version of the initial printed report [Limbach,P.A., Crain,P.F. and McCloskey,J.A. (1994)Nucleic Acids Res. , 22, 2183-2196]. Information provided for each nucleoside includes: the RNA in which it occurs and phylogenetic distribution; common chemical name and symbol; Chemical Abstracts registry number and index name; chemical structure; initial literature citations for structural characterization or occurrence, and for chemical synthesis. The data are available through the WWW and via anonymous ftp.

Databases, Factual↗

PubMed1991

Blocking of Tat-dependent HIV-1 RNA modification by an inhibitor of RNA polymerase II processivity.

Human immunodeficiency virus gene expression is regulated transcriptionally and post-transcriptionally by the virally encoded tat protein (Tat). Tat functions through an RNA target sequence located in the untranslated region at the 5' end of viral transcripts. In Xenopus oocytes, translation of RNA containing the target sequence is specifically activated by Tat. This activation only occurs if the RNA is injected into the nucleus, and might be due to Tat-dependent, nucleus-specific chemical modification of the RNA which somehow facilitates translation. Here we demonstrate that Tat activation of its target RNA in the nucleus involves a Tat-dependent covalent modification. The modified RNA is competent for translation after reinjection into either the nucleus or the cytoplasm in the absence of Tat. Furthermore, we find that the nucleoside analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, which inhibits processivity of RNA polymerase II (ref. 9), blocks this Tat-dependent modification.

Animals↗

PubMed1998

The RNA modification database--1998.

The RNA modification database provides a comprehensive listing of posttranscriptionally modified nucleosides from RNA, and is maintained as an updated version of the initial printed report [Limbach,P.A., Crain,P.F. and McCloskey,J.A. (1994) Nucleic Acids Res. , 22, 2183-2196]. Information provided for each nucleoside includes: the type of RNA in which it occurs and phylogenetic distribution; common chemical name and symbol; Chemical Abstracts registry number and index name; chemical structure; initial literature citations for structural characterization or occurrence, and for chemical synthesis. The data are available through the World Wide Web at: http://www-medlib.med.utah/RNAmods/RNAmods .html

Computer Communication Networks↗

PubMed1996

The neurofibromatosis type I messenger RNA undergoes base-modification RNA editing.

A functional mooring sequence, known to be required for apolipoprotein B (apoB) mRNA editing, exists in the mRNA encoding the neurofibromatosis type I (NF1) tumor suppressor. Editing of NF1 mRNA modifies cytidine in an arginine codon (CGA) at nucleotide 2914 to a uridine (UGA), creating an in frame translation stop codon. NF1 editing occurs in normal tissue but was several-fold higher in tumors. In vitro editing and transfection assays demonstrated that apoB and NF1 RNA editing will take place in both neural tumor and hepatoma cells. Unlike apoB, NF1 editing did not demonstrate dependence on rate-limiting quantities of APOBEC-1 (the apoB editing catalytic subunit) suggesting that different trans-acting factors may be involved in the two editing processes.

Apolipoproteins B↗

PubMed2006

Involvement of the Escherichia coli folate-binding protein YgfZ in RNA modification and regulation of chromosomal replication initiation.

The Escherichia coli hda gene codes for a DnaA-related protein that is essential for the regulatory inactivation of DnaA (RIDA), a system that controls the initiation of chromosomal replication. We have identified the ygfZ gene, which encodes a folate-binding protein, as a suppressor of hda mutations. The ygfZ null mutation suppresses an hda null mutation. The over-initiation and abortive elongation phenotypes conferred by the hda mutations are partially suppressed in an hda ygfZ background. The accumulation of the active form of DnaA, ATP-DnaA, in the hda mutant is suppressed by the disruption of the ygfZ gene, indicating that YgfZ is involved in regulating the level of ATP-DnaA. Although ygfZ is not an essential gene, the ygfZ disruptant grows slowly, especially at low temperature, demonstrating that this gene is important for cellular proliferation. We have identified mnmE (trmE) as a suppressor of the ygfZ disruption. This gene encodes a GTPase involved in tRNA modification. Examination of RNA modification in the ygfZ mutant reveals reduced levels of 2-methylthio N(6)-isopentenyladenosine [corrected] indicating that YgfZ participates in the methylthio-group formation of this modified nucleoside in some tRNAs. These results suggest that YgfZ is a key factor in regulatory networks that act via tRNA modification.

Bacterial Proteins↗

PubMed1999

The RNA Modification Database: 1999 update.

The RNA Modification Database (http://medlib.med.utah.edu/RNAmods/) provides a comprehensive listing of naturally modified nucleosides in RNA. Each file includes: chemical structure; common name and symbol; type(s) of RNA in which found and corresponding phylogenetic distribution; Chemical s registry number and index name; and initial literature citations for structure characterization and chemical synthesis. New features include capability to search database files by name or substructural features, modifications in tmRNA, and links to related data and sites.

Archaea↗

PubMed1994

Fluorescence postlabeling assay of RNA modification.

A new approach has been developed to assay RNA modification by combining enzymatic digestion of RNA to nucleoside monophosphate and fluorescence postlabeling. Nuclease P1 digestion of modified RNA affords both normal and modified nucleotides. The nucleotides are labeled in-situ with dansyl chloride via phosphoramidate derivatives with ethylenediamine following a procedure initially designed to synthesize fluorescence labeled deoxynucleotides. The postlabeled nucleotides are analyzed by HPLC using a fluorescence detector. Fluorescence postlabeling assay of 7-methylGmp in RNA exposed to dimethyl sulfate has validated the technique. In the presence of excess normal nucleotides, the limit of detection (LOD) lies between normal to modified nucleotide ratio of 10(3) to 10(4). HPLC enrichment of the modified nucleotide from the normal nucleotides prior to labeling enhances the LOD by two orders of magnitude.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

[Identification of RNA modification enzymes using sequence homology].

Modified nucleotides possessing diverse chemical structures are universally present in all cell RNAs. Their formation is a posttranscriptional process catalyzed by various RNA modification enzymes. Despite the large body of data concerning the localization of modified nucleotides in different RNAs, the enzymes involved in their biosynthesis remain largely unknown. In this review we discuss the recent achievements in application of the sequence homology approach to searching for and identifying RNA modification enzymes such as RNA-pseudouridine synthases, RNA-methyltransferases, and RNA-inosine synthases (adenosine deaminases).

Animals↗

PubMed1999

Transfer RNA modification: influence on translational frameshifting and metabolism.

Transfer RNA modification improves the rate of aa-tRNA selection at the A-site and the fitness in the P-site and thereby prevents frameshifting according to a new model how frameshifting occurs [Qian et al. (1998) Mol. Cell 1, 471-482]. Evidence that the presence of various modified nucleosides in tRNA also influences central metabolism, thiamine metabolism, and bacterial virulence is reviewed.

Frameshifting, Ribosomal↗

PubMed2026

m6A RNA modification and its emerging roles in diseases: recent advances and therapeutic implications.

BACKGROUND: In the recent past, insights in post transcriptional regulation of gene expression have profoundly reshaped our understanding of the molecular mechanisms underlying health and disease. This paradigm shift largely stems from the emerging field of epitranscriptomics, which highlights the pivotal role of chemical RNA modifications. While more than 170 distinct chemical modifications on the RNA are known, the m6A modification is the most abundant internal mRNA modification in higher eukaryotic cells, present not only on protein coding transcripts but also on non-coding RNAs, regulated by “writers”, “erasers”, and “readers” that together modulate alternative splicing, nuclear export, translation efficiency, and mRNA stability. MAIN BODY: This review addresses an important gap by presenting a multilayered regulatory framework that catalogs the full repertoire of m6A machinery and uniquely reveals how non-coding RNAs, transcription factors, histone modifications, and chromatin remodelers governs the spatiotemporal specificity of m6A modification. We explore how dysregulation of m6A modification and its regulatory proteins contribute to the development and progression of various diseases such as cardiovascular disease, neurological disorders, cancer, and type 2 diabetes through context-dependent modulation of gene networks. Furthermore, we present an integrative overview of the therapeutic pipeline, tracing the development of small-molecule inhibitors targeting m6A regulators, thus bridging a crucial link between fundamental mechanisms and new therapies. CONCLUSIONS: Overall, this review integrates current findings and emerging insights to provide a comprehensive understanding of m6A biology. By linking upstream regulatory mechanisms with downstream pathological consequences and therapeutic interventions, we highlight the potential of targeting the epitranscriptome for clinical applications.

Humans↗

PubMed2006

MODOMICS: a database of RNA modification pathways.

MODOMICS is the first comprehensive database resource for systems biology of RNA modification. It integrates information about the chemical structure of modified nucleosides, their localization in RNA sequences, pathways of their biosynthesis and enzymes that carry out the respective reactions. MODOMICS also provides literature information, and links to other databases, including the available protein sequence and structure data. The current list of modifications and pathways is comprehensive, while the dataset of enzymes is limited to Escherichia coli and Saccharomyces cerevisiae and sequence alignments are presented only for tRNAs from these organisms. RNAs and enzymes from other organisms will be included in the near future. MODOMICS can be queried by the type of nucleoside (e.g. A, G, C, U, I, m1A, nm5s2U, etc.), type of RNA, position of a particular nucleoside, type of reaction (e.g. methylation, thiolation, deamination, etc.) and name or sequence of an enzyme of interest. Options for data presentation include graphs of pathways involving the query nucleoside, multiple sequence alignments of RNA sequences and tabular forms with enzyme and literature data. The contents of MODOMICS can be accessed through the World Wide Web at http://genesilico.pl/modomics/.

Base Sequence↗

PubMed2005

Transglycosylation: a mechanism for RNA modification (and editing?).

The vast majority of the ca. 100 chemically distinct modified nucleosides in RNA appear to arise via the chemical transformation of a genetically encoded nucleoside. Two notable exceptions are queuosine and pseudouridine, which are incorporated into tRNA via transglycosylation. Transglycosylation is an extremely efficient process for incorporating highly modified bases such as queuine into RNA. Transglycosylation is also a requisite process for "isomerizing" an N-nucleoside into a C-nucleoside as is the case for pseudouridine formation. Finally, transglycosylation is an attractive possibility for certain RNA editing events (e.g., pyrimidine to purine conversions) that cannot occur via the known, more straightforward enzymatic reactions (e.g., deaminations). This review discusses what is known about the mechanisms of transglycosylation for the queuine and pseudouridine RNA modifications and will speculate about a potential role for transglycosylation in certain RNA editing events.

Crystallography, X-Ray↗

PubMed1994

Specific detection of positive and negative stranded hepatitis C viral RNA using chemical RNA modification.

Since hepatitis C virus (HCV), a major causative agent of posttransfusional non-A, non-B hepatitis, is a positive stranded RNA virus, it is supposed to replicate via a negative RNA strand. Although strand specific reverse transcription-polymerase chain reaction (RT-PCR) method was recently developed to detect each strand of HCV RNA, the specificity of the strategy has remained to be determined. In this study, using in vitro transcribed positive and negative stranded HCV RNAs mixed with hepatic cellular RNA from normal liver, we found that this strategy did not distinguish between the two RNA strands, but that chemical modification of RNA samples at the 3' end followed by strand specific RT-PCR made specific detection possible. Liver tissues, sera and peripheral blood mononuclear cells (PBMC) from ten patients with chronic HCV infection were analyzed with the novel strategy of RT-PCR combined with RNA modification. Positive and negative strands of HCV RNA were detected in liver tissues of ten (100%) and nine (90%) cases, respectively. Negative RNA strand was detected also in sera of five cases (50%), positive strand being detected in nine cases (90%). In PBMC, positive strand of HCV RNA was detected in eight cases (80%), whereas negative strand in only one case (10%), suggesting that HCV has much less cellular tropism to PBMC than to hepatocytes.

Adult↗