The Roles of Host 5-Methylcytosine RNA Methyltransferases during Viral Infections

Wnuk, Maciej; Slipek, Piotr; Dziedzic, Mateusz; Lewińska, Anna

doi:10.3390/ijms21218176

Cited by 29 publications

(26 citation statements)

References 124 publications

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“…We next investigated the conservation of 83 RNA modification sites previously reported in two studies, 42 having 5-methylcytosine (m 5 C) modifications 25 and 41 having RNA modifications of unidentified type 24 . RNA modifications such as m 5 C and N6-methyladenosine (m 6 A) can be detected using direct RNA sequencing 84 , and are known to play a role in regulation of replication and packaging of RNA viruses, as well as host response 85,86 .…”

Section: Nucleotides Upstream Of Orf1a)mentioning

confidence: 99%

SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes

2021

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Despite its clinical importance, the SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. We use comparative genomics to provide a high-confidence protein-coding gene set, characterize evolutionary constraint, and prioritize functional mutations. We select 44 Sarbecovirus genomes at ideally-suited evolutionary distances, and quantify protein-coding evolutionary signatures and overlapping constraint. We find strong protein-coding signatures for ORFs 3a, 6, 7a, 7b, 8, 9b, and a novel alternate-frame gene, ORF3c, whereas ORFs 2b, 3d/3d-2, 3b, 9c, and 10 lack protein-coding signatures or convincing experimental evidence of protein-coding function. Furthermore, we show no other conserved protein-coding genes remain to be discovered. Mutation analysis suggests ORF8 contributes to within-individual fitness but not person-to-person transmission. Cross-strain and within-strain evolutionary pressures agree, except for fewer-than-expected within-strain mutations in nsp3 and S1, and more-than-expected in nucleocapsid, which shows a cluster of mutations in a predicted B-cell epitope, suggesting immune-avoidance selection. Evolutionary histories of residues disrupted by spike-protein substitutions D614G, N501Y, E484K, and K417N/T provide clues about their biology, and we catalog likely-functional co-inherited mutations. Previously reported RNA-modification sites show no enrichment for conservation. Here we report a high-confidence gene set and evolutionary-history annotations providing valuable resources and insights on SARS-CoV-2 biology, mutations, and evolution.

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Section: Nucleotides Upstream Of Orf1a)mentioning

confidence: 99%

SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes

2021

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“…The regulation of m 5 C modifications during virus replication provides new insights into viral pathology and suggests the potential of m 5 C methylase inhibitors as antiviral drugs. 189…”

Section: Virusesmentioning

confidence: 99%

Advances in mRNA 5-methylcytosine modifications: Detection, effectors, biological functions, and clinical relevance

Guo

Pan

et al. 2021

Molecular Therapy - Nucleic Acids

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5-methylcytosine (m 5 C) post-transcriptional modifications affect the maturation, stability, and translation of the mRNA molecule. These modifications play an important role in many physiological and pathological processes, including stress response, tumorigenesis, tumor cell migration, embryogenesis, and viral replication. Recently, there has been a better understanding of the biological implications of m 5 C modification owing to the rapid development and optimization of detection technologies, including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA-BisSeq. Further, predictive models (such as PEA-m 5 C, m 5 C-PseDNC, and DeepMRMP) for the identification of potential m 5 C modification sites have also emerged. In this review, we summarize the current experimental detection methods and predictive models for mRNA m 5 C modifications, focusing on their advantages and limitations. We systematically surveyed the latest research on the effectors related to mRNA m 5 C modifications and their biological functions in multiple species. Finally, we discuss the physiological effects and pathological significance of m 5 C modifications in multiple diseases, as well as their therapeutic potential, thereby providing new perspectives for disease treatment and prognosis.

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“…Furthermore, RNA methylations exist in many RNA species. For example, besides mRNA, m5C also exists in ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and some non-coding RNAs ( Bohnsack et al, 2019 ; Wnuk et al, 2020 ). In addition to the m1A in mRNAs, this RNA modification is also crucial for the stability of tRNA.…”

Section: Rna Methylationmentioning

confidence: 99%

RNA Methylations in Cardiovascular Diseases, Molecular Structure, Biological Functions and Regulatory Roles in Cardiovascular Diseases

et al. 2021

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the world. Despite considerable progress in the diagnosis, treatment and prognosis of CVDs, new diagnostic biomarkers and new therapeutic measures are urgently needed to reduce the mortality of CVDs and improve the therapeutic effect. RNA methylations regulate almost all aspects of RNA processing, such as RNA nuclear export, translation, splicing and non-coding RNA processing. In view of the importance of RNA methylations in the pathogenesis of diseases, this work reviews the molecular structures, biological functions of five kinds of RNA methylations (m6A, m5C, m1a, m6am and m7G) and their effects on CVDs, including pulmonary hypertension, hypertension, vascular calcification, cardiac hypertrophy, heart failure. In CVDs, m6A “writers” catalyze the installation of m6A on RNAs, while “erasers” remove these modifications. Finally, the “readers” of m6A further influence the mRNA splicing, nuclear export, translation and degradation. M5C, m1A, m6Am and m7G are new types of RNA methylations, their roles in CVDs need to be further explored. RNA methylations have become a new research hotspot and the roles in CVDs is gradually emerging, the review of the molecular characteristics, biological functions and effects of RNA methylation on CVDs will contribute to the elucidation of the pathological mechanisms of CVDs and the discovery of new diagnostic markers and therapeutic targets of CVDs.

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The Roles of Host 5-Methylcytosine RNA Methyltransferases during Viral Infections

Cited by 29 publications

References 124 publications

SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes

SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes

Advances in mRNA 5-methylcytosine modifications: Detection, effectors, biological functions, and clinical relevance

RNA Methylations in Cardiovascular Diseases, Molecular Structure, Biological Functions and Regulatory Roles in Cardiovascular Diseases

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