Reversible RNA Modification<i>N</i>1-Methyladenosine (m1A) in mRNA and tRNA

Zhang, Chi; Jia, Guifang

doi:10.1016/j.gpb.2018.03.003

Cited by 158 publications

(140 citation statements)

References 50 publications

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“…N 1 -methyladenosine (m 1 A) is a reversible modification in tRNA, mRNA and lncRNAs, even in mitochondrial transcripts, and is critical for tRNA stability, and translation of mitochondrial DNA-encoded proteins [134]. In nucleus, m 1 A modifications in pre-tRNA and pre-mRNA are catalyzed by tRNA methyltransferase 6/61A (TRMT6-TRMT61A) catalytic complex and are erased by ALKBH1 and ALKBH3, respectively [135,136].…”

Section: Rna M 1 a Modification In Gbmmentioning

confidence: 99%

The Emerging Roles of RNA Modifications in Glioblastoma

Dong

Cui

2020

Cancers

103

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Glioblastoma (GBM) is a grade IV glioma that is the most malignant brain tumor type. Currently, there are no effective and sufficient therapeutic strategies for its treatment because its pathological mechanism is not fully characterized. With the fast development of the Next Generation Sequencing (NGS) technology, more than 170 kinds of covalent ribonucleic acid (RNA) modifications are found to be extensively present in almost all living organisms and all kinds of RNAs, including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and messenger RNAs (mRNAs). RNA modifications are also emerging as important modulators in the regulation of biological processes and pathological progression, and study of the epi-transcriptome has been a new area for researchers to explore their connections with the initiation and progression of cancers. Recently, RNA modifications, especially m6A, and their RNA-modifying proteins (RMPs) such as methyltransferase like 3 (METTL3) and α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), have also emerged as important epigenetic mechanisms for the aggressiveness and malignancy of GBM, especially the pluripotency of glioma stem-like cells (GSCs). Although the current study is just the tip of an iceberg, these new evidences will provide new insights for possible GBM treatments. In this review, we summarize the recent studies about RNA modifications, such as N6-methyladenosine (m6A), N6,2′O-dimethyladenosine (m6Am), 5-methylcytosine (m5C), N1-methyladenosine (m1A), inosine (I) and pseudouridine (ψ) as well as the corresponding RMPs including the writers, erasers and readers that participate in the tumorigenesis and development of GBM, so as to provide some clues for GBM treatment.

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Section: Rna M 1 a Modification In Gbmmentioning

confidence: 99%

The Emerging Roles of RNA Modifications in Glioblastoma

Dong

Cui

2020

Cancers

103

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“…Different organs of the leaves, flowers and roots have differential m 6 A methylation, suggesting that m 6 A methylation plays an important role during development and differentiation (Wang et al, 2017). Besides which, more than 20 m 1 A sites are also identified in mitochondrial genes via using a transcriptome-wide analysis (Zhang and Jia, 2018). These findings unravel a new concept of mitoepitranscriptome, referring to dynamic regulation of gene expression by the modified mtRNAs.…”

Section: Mtrna Modificationsmentioning

confidence: 73%

Mitoepigenetics and Its Emerging Roles in Cancer

Dong

Cui

2020

Front. Cell Dev. Biol.

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In human beings, there is a ∼16,569 bp circular mitochondrial DNA (mtDNA) encoding 22 tRNAs, 12S and 16S rRNAs, 13 polypeptides that constitute the central core of ETC/OxPhos complexes, and some non-coding RNAs. Recently, mtDNA has been shown to have some covalent modifications such as methylation or hydroxylmethylation, which play pivotal epigenetic roles in mtDNA replication and transcription. Posttranslational modifications of proteins in mitochondrial nucleoids such as mitochondrial transcription factor A (TFAM) also emerge as essential epigenetic modulations in mtDNA replication and transcription. Post-transcriptional modifications of mitochondrial RNAs (mtRNAs) including mt-rRNAs, mt-tRNAs and mt-mRNAs are important epigenetic modulations. Besides, mtDNA or nuclear DNA (n-DNA)-derived non-coding RNAs also play important roles in the regulation of translation and function of mitochondrial genes. These evidences introduce a novel concept of mitoepigenetics that refers to the study of modulations in the mitochondria that alter heritable phenotype in mitochondria itself without changing the mtDNA sequence. Since mitochondrial dysfunction contributes to carcinogenesis and tumor development, mitoepigenetics is also essential for cancer. Understanding the mode of actions of mitoepigenetics in cancers may shade light on the clinical diagnosis and prevention of these diseases. In this review, we summarize the present study about modifications in mtDNA, mtRNA and nucleoids and modulations of mtDNA/nDNA-derived non-coding RNAs that affect mtDNA translation/function, and overview recent studies of mitoepigenetic alterations in cancer.

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“…Recent methodological advances have demonstrated that m1A is a transcriptome-wide modification [172,173]. Several members of the TRMT family (tRNA methyltransferase family) have already been shown to be m1A writers and additional writers are thought to exist [172][173][174]. Similar to m6A, m1A is reversible and can be demethylated by erasers ALKBH1 and 3 (alkB homolog 1 and 3) [173,175].…”

Section: N1-methyladenosine (M1a)mentioning

confidence: 99%

An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

Kwast

Quax

Nossent

2019

Cells

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Therapeutic neovascularization can facilitate blood flow recovery in patients with ischemic cardiovascular disease, the leading cause of death worldwide. Neovascularization encompasses both angiogenesis, the sprouting of new capillaries from existing vessels, and arteriogenesis, the maturation of preexisting collateral arterioles into fully functional arteries. Both angiogenesis and arteriogenesis are highly multifactorial processes that require a multifactorial regulator to be stimulated simultaneously. MicroRNAs can regulate both angiogenesis and arteriogenesis due to their ability to modulate expression of many genes simultaneously. Recent studies have revealed that many microRNAs have variants with altered terminal sequences, known as isomiRs. Additionally, endogenous microRNAs have been identified that carry biochemically modified nucleotides, revealing a dynamic microRNA epitranscriptome. Both types of microRNA alterations were shown to be dynamically regulated in response to ischemia and are able to influence neovascularization by affecting the microRNA’s biogenesis, or even its silencing activity. Therefore, these novel regulatory layers influence microRNA functioning and could provide new opportunities to stimulate neovascularization. In this review we will highlight the formation and function of isomiRs and various forms of microRNA modifications, and discuss recent findings that demonstrate that both isomiRs and microRNA modifications directly affect neovascularization and vascular remodeling.

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Reversible RNA ModificationN1-Methyladenosine (m1A) in mRNA and tRNA

Cited by 158 publications

References 50 publications

The Emerging Roles of RNA Modifications in Glioblastoma

The Emerging Roles of RNA Modifications in Glioblastoma

Mitoepigenetics and Its Emerging Roles in Cancer

An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

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