Technical challenges in defining RNA modifications

Huang, Gefei; Ding, Qiutao; Xie, Dongying; Cai, Zongwei; Zhao, Zhongying

doi:10.1016/j.semcdb.2021.11.009

Cited by 9 publications

(6 citation statements)

References 102 publications

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“…It is well known that mRNA synthesis, its post-transcriptional modification, and its translation into proteins are complicated processes in vivo . [ 66 , 73 , 74 ] DUBs have been reported to be involved in gene transcription regulation. [ 43 ] For example, USP12 aggravates angiotensin II (Ang II)-induced cardiac hypertrophy by enhancing methyltransferase-like 3 (METTL3) expression, which catalyzes N6-methyladenosine modification of mRNA and acts as a harmful factor in pathological cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

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Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners

Zhao

Zheng

Wang

et al. 2022

Chinese Medical Journal

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Background:Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated.Methods:Immunoblotting, real-time polymerase chain reaction, in vivo/in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4+ T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data).Results:The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression (r = 0.5110) and CD4+ T-cell counts (r = 0.5083) in HIV-1-infected patients.Conclusions:USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections.

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Section: Discussionmentioning

confidence: 99%

“…Further investigation showed that USP3 and USP3 mutants interacted with A3G mRNA. It is well known that mRNA synthesis, its post-transcriptional modification, and its translation into proteins are complicated processes in vivo [66,73,74] . DUBs have been reported to be involved in gene transcription regulation [43] .…”

Section: Discussionmentioning

confidence: 99%

Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners

Zhao

Zheng

Wang

et al. 2022

Chinese Medical Journal

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“…While the Nanopore platform has demonstrated its ability to detect various nucleic acid modifications, such as 5mC, 5hmC in DNA and m 6 A, m 5 C in RNA [151][152][153][154][155][156][157], the SMRT platform exhibits promise in the identification of RNA modification (m 6 A) through the analysis of fluorescent signal alterations during reverse transcription. However, its reliability currently remains limited [158,159]. While they hold great potential for epigenomic and epitranscriptomic sequencing, at present, significant challenges and limitations remain, including high error rate, high cost, and high-sample input requirement.…”

Section: Third Generation Sequencing For Dna and Rna Modificationsmentioning

confidence: 99%

Mapping epigenetic modifications by sequencing technologies

Chen,

Xu,

Shu

et al. 2023

Cell Death Differ

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The “epigenetics” concept was first described in 1942. Thus far, chemical modifications on histones, DNA, and RNA have emerged as three important building blocks of epigenetic modifications. Many epigenetic modifications have been intensively studied and found to be involved in most essential biological processes as well as human diseases, including cancer. Precisely and quantitatively mapping over 100 [1], 17 [2], and 160 [3] different known types of epigenetic modifications in histone, DNA, and RNA is the key to understanding the role of epigenetic modifications in gene regulation in diverse biological processes. With the rapid development of sequencing technologies, scientists are able to detect specific epigenetic modifications with various quantitative, high-resolution, whole-genome/transcriptome approaches. Here, we summarize recent advances in epigenetic modification sequencing technologies, focusing on major histone, DNA, and RNA modifications in mammalian cells.

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“…It has emerged as a central player in gene expression control and is increasingly recognized for its contributions to various physiological and pathological processes, including cancer. Understanding the nuances of RNA m6A modification is fundamental to unraveling its implications in cancer biology and holds promise for novel therapeutic avenues in oncology [4].…”

Section: Defining Rna M6a Modificationmentioning

confidence: 99%

RNA m6A Modifications and Cancer

Afrasiyab,

Sadaf,

Peilin

et al. 2023

Int J Oncol Res

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Epitranscriptomic modifications of RNA, particularly N6methyladenosine (m6A), have emerged as pivotal players in cancer biology. RNA m6A modifications dynamically regulate gene expression, influencing various aspects of RNA processing, stability, and translation. In the context of cancer, dysregulation of RNA m6A modification has been implicated in tumorigenesis, metastasis, therapy resistance, and the tumor micro environment. This review provides an indepth exploration of the intricate relationship between RNA m6A modifications and cancer. It comprehensively outlines the enzymatic machinery responsible for m6A deposition, removal, and recognition, emphasizing how alterations in these processes contribute to oncogenesis. Global profiling techniques have revealed specific m6A patterns in various cancer types, shedding light on potential diagnostic and prognostic biomarkers. Functional insights into RNA m6A modifications underscore their impact on RNA metabolism and gene expression, influencing key oncogenic signaling pathways. Moreover, the clinical relevance of RNA m6A modifications in cancer is discussed, highlighting their potential as therapeutic targets and biomarkers for personalized medicine. This review also delves into the emerging role of RNA m6A modifications in cancer stem cells, tumor microenvironment interactions, and their crosstalk with other epigenetic marks, providing a holistic view of their contributions to cancer pathobiology. Furthermore, it discusses ongoing research, technological advancements, and future prospects in this rapidly evolving field.In summary, this comprehensive review illuminates the multifaceted landscape of RNA m6A modifications in cancer, offering valuable insights into their diagnostic, prognostic, and therapeutic implications. Understanding the complex interplay between RNA m6A modifications and cancer biology is essential for harnessing their potential for precision oncology and novel therapeutic interventions.

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Technical challenges in defining RNA modifications

Cited by 9 publications

References 102 publications

Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners

Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners

Mapping epigenetic modifications by sequencing technologies

RNA m6A Modifications and Cancer

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