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Virology Journal Nov 2019N6-methyladenosine (m6A) modification is the most prevalent internal modification of eukaryotic mRNA modulating gene expression. m6A modification is a dynamic reversible... (Review)
Review
BACKGROUND
N6-methyladenosine (m6A) modification is the most prevalent internal modification of eukaryotic mRNA modulating gene expression. m6A modification is a dynamic reversible process regulated by three protein groups: methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). m6A modification is involved in all phases of RNA metabolism, including RNA folding, stability, splicing, nuclear exporting, translational modulation and degradation.
MAIN BODY
In recent years, numerous studies have reported that abnormal m6A modification causes aberrant expression of important viral genes. Herein, we review the role of m6A in viral lifecycle and its contribution to the pathogenesis of human diseases. Particularly, we focus on the viruses associated with human diseases such as HIV-1, IAV, HBV, HCV, EBV and many others.
CONCLUSIONS
A better understanding of m6A-virus relationship would provide new insights into the viral replication process and pathogenesis of human diseases caused by viruses. In addition, exploration of the role of m6A in disease-causing viruses will reveal novel approaches for the treatment of such diseases.
Topics: Adenosine; Animals; Gene Expression Regulation, Viral; Humans; RNA Processing, Post-Transcriptional; RNA, Viral; Virus Diseases; Virus Physiological Phenomena; Virus Replication; Viruses
PubMed: 31711514
DOI: 10.1186/s12985-019-1236-3 -
Anesthesiology Jul 2021
Topics: Humans; Adenosine; Hypoxia; Inflammation
PubMed: 34046661
DOI: 10.1097/ALN.0000000000003841 -
Medical Science Monitor : International... Apr 2020According to the World Health Organization cardiovascular disease risk charts, the mortality rate of cardiovascular diseases in people is still high. The medical... (Review)
Review
According to the World Health Organization cardiovascular disease risk charts, the mortality rate of cardiovascular diseases in people is still high. The medical expenses caused by cardiovascular diseases are increasing daily, and the medical burden is becoming heavier; as such, it is imperative to prevent and cure cardiovascular diseases. A large number of scholars are analyzing the pathogenesis of cardiovascular diseases from various perspectives. Recent findings suggest that N6-methyladenosine (m6A) plays a multifaceted role in the cardiovascular system. m6A is a methylated modification product on RNA molecules and exists on various RNA molecules. It is one of the most common epigenetic modifications discovered to date. It regulates the expression of genes and subsequent responses. The amount of m6A is determined by methylases (writers) and demethylases (erasers). The third type of proteins, readers, selectively bind to m6A to regulate RNA stability and gene expression. In this paper, the relationship between m6A and related enzymes and cardiovascular structure and function was reviewed based on recent research results regarding the cardiovascular system.
Topics: Adenosine; Cardiovascular Diseases; Cardiovascular System; Epigenesis, Genetic; Gene Expression; Humans; Lipid Metabolism; Lipids; Methylation; Methyltransferases
PubMed: 32350237
DOI: 10.12659/MSM.921742 -
Frontiers in Immunology 2023
Topics: Humans; Adenosine; Immunotherapy; Neoplasms
PubMed: 37885877
DOI: 10.3389/fimmu.2023.1298487 -
Nature Jun 2020The nature of the first genetic polymer is the subject of major debate. Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of...
The nature of the first genetic polymer is the subject of major debate. Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of the prebiotic era-that is, prior to the dawn of life-other evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA. Such a theory streamlines the eventual 'genetic takeover' of homogeneous DNA from RNA as the principal information-storage molecule, but requires a selective abiotic synthesis of both RNA and DNA building blocks in the same local primordial geochemical scenario. Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purine deoxyribonucleosides: deoxyadenosine and deoxyinosine. Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purine deoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine and uridine. These results support the notion that purine deoxyribonucleosides and pyrimidine ribonucleosides may have coexisted before the emergence of life.
Topics: Adenosine; Cytidine; DNA; Evolution, Chemical; Origin of Life; Oxidation-Reduction; Purine Nucleosides; Pyrimidine Nucleosides; RNA; Uridine
PubMed: 32494078
DOI: 10.1038/s41586-020-2330-9 -
Frontiers in Bioscience (Landmark... Oct 2023Metazoan adenosine-to-inosine (A-to-I) RNA editing is a highly conserved mechanism that diversifies the transcriptome by post-transcriptionally converting adenosine to... (Review)
Review
Metazoan adenosine-to-inosine (A-to-I) RNA editing is a highly conserved mechanism that diversifies the transcriptome by post-transcriptionally converting adenosine to inosine. Millions of editing sites have been identified in different species and, based on abnormal editing observed in various disorders, it is intuitive to conclude that RNA editing is both functional and adaptive. In this review, we propose the following major points: (1) "Function/functional" only represents a molecular/phenotypic consequence and is not necessarily connected to "adaptation/adaptive"; (2) Adaptive editing should be judged in the light of evolution and emphasize advantages of temporal-spatial flexibility; (3) Adaptive editing could, in theory, be extended from nonsynonymous sites to all potentially functional sites. This review seeks to conceptually bridge the gap between molecular biology and evolutionary biology and provide a more objective understanding on the biological functions and evolutionary significance of RNA editing.
Topics: Animals; RNA; RNA Editing; Adenosine; Inosine; Transcriptome
PubMed: 37919076
DOI: 10.31083/j.fbl2810256 -
Frontiers in Cellular and Infection... 2020N6-methyladenosine (mA) is the most prevalent and internal modification of eukaryotic mRNA. Multiple mA methylation sites have been identified in the viral RNA genome... (Review)
Review
N6-methyladenosine (mA) is the most prevalent and internal modification of eukaryotic mRNA. Multiple mA methylation sites have been identified in the viral RNA genome and transcripts of DNA viruses in recent years. mA modification is involved in all the phases of RNA metabolism, including RNA stability, splicing, nuclear exporting, RNA folding, translational modulation, and RNA degradation. Three protein groups, methyltransferases (mA-writers), demethylases (mA-erasers), and mA-binding proteins (mA-readers) regulate this dynamic reversible process. Here, we have reviewed the role of mA modification dictating viral replication, morphogenesis, life cycle, and its contribution to disease progression. A better understanding of the mA methylation process during viral pathogenesis is required to reveal novel approaches to combat the virus-associated diseases.
Topics: Adenosine; Methylation; Methyltransferases; RNA, Viral
PubMed: 33330128
DOI: 10.3389/fcimb.2020.584283 -
Cancer Gene Therapy Sep 2020Epigenetic mRNA modification is an evolving field. N-methyladenosine (mA) is the most frequent internal transcriptional modification in eukaryotic messenger RNAs... (Review)
Review
Epigenetic mRNA modification is an evolving field. N-methyladenosine (mA) is the most frequent internal transcriptional modification in eukaryotic messenger RNAs (mRNAs). This review will discuss the functions of the mA mRNA machinery, including its "writers" that are components of the methyltransferase complex, its "readers" and its "erasers" (specifically FTO and ALKBH5) in cancer. The writers deposit the mA and include METTL3, METTL14, WTAP, VIRMA, and RBM15. MA methylation is removed by the m6A demethylases (FTO and ALKBH5). Lastly, the most diverse members are the readers that can contribute to mRNA splicing, stability, translation, and nuclear export. Many of these functions continue to be elucidated. The dysregulation of this machinery in various malignancies and the associated impact on tumorigenesis and drug response will be discussed herein with a focus on solid tumors. It is clear that, by contributing to either mRNA stability or translation, there are downstream targets that are impacted, contributing to cancer progression and the self-renewal ability of cancer stem cells.
Topics: Adenosine; Epigenesis, Genetic; Humans; Neoplasms; RNA
PubMed: 31956264
DOI: 10.1038/s41417-020-0160-4 -
Nature Communications Mar 2022RNA editing by adenosine deaminases changes the information encoded in the mRNA from its genomic blueprint. Editing of protein-coding sequences can introduce novel,...
RNA editing by adenosine deaminases changes the information encoded in the mRNA from its genomic blueprint. Editing of protein-coding sequences can introduce novel, functionally distinct, protein isoforms and diversify the proteome. The functional importance of a few recoding sites has been appreciated for decades. However, systematic methods to uncover these sites perform poorly, and the full repertoire of recoding in human and other mammals is unknown. Here we present a new detection approach, and analyze 9125 GTEx RNA-seq samples, to produce a highly-accurate atlas of 1517 editing sites within the coding region and their editing levels across human tissues. Single-cell RNA-seq data shows protein recoding contributes to the variability across cell subpopulations. Most highly edited sites are evolutionary conserved in non-primate mammals, attesting for adaptation. This comprehensive set can facilitate understanding of the role of recoding in human physiology and diseases.
Topics: Adenosine; Animals; Genome; Humans; Inosine; Mammals; RNA; RNA Editing
PubMed: 35246538
DOI: 10.1038/s41467-022-28841-4 -
Current Opinion in Structural Biology Aug 2021RNA undergoes extensive biochemical modification following transcription. In addition to RNA splicing, transcripts are processed by a suite of enzymes that alter the... (Review)
Review
RNA undergoes extensive biochemical modification following transcription. In addition to RNA splicing, transcripts are processed by a suite of enzymes that alter the chemical structure of different nucleobases. Broadly termed as 'RNA editing,' these modifications impart significant functional changes to translation, localization, and stability of individual transcripts within the cell. These changes are dynamic and required for a number of critical cellular processes, and dysregulation of these pathways is responsible for several disease states. Accurately detecting, measuring, and mapping different RNA modifications across the transcriptome is vital to understanding their broader functions as well as leveraging these events as diagnostic biomarkers. Here, we review recent advances in profiling several types of RNA modifications, with particular emphasis on adenosine-to-inosine (A-to-I) and N-methyladenosine (mA) RNA editing. We especially highlight approaches that utilize proteins to detect or enrich modified RNA transcripts before sequencing, and we summarize recent insights yielded from these techniques.
Topics: Adenosine; Inosine; RNA; RNA Editing; Transcriptome
PubMed: 33445115
DOI: 10.1016/j.sbi.2020.12.006