N6-Methyladenosines Modulate A-to-I RNA Editing

Xiang, Jianfeng; Yang, Qin; Liu, Chu-Xiao; Wu, Man; Chen, Lingling; Yang, Li

doi:10.1016/j.molcel.2017.12.006

Cited by 118 publications

(100 citation statements)

References 41 publications

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“…Moreover, one should never overlook that a crosstalk may exist between different epitranscriptomic modifiers affecting the same transcripts, as shown, for example, between the A to I RNA editing enzyme ADAR1 and m 6 A methylation. In specific transcripts, in fact, the association of ADAR1 was shown to be impaired by m 6 A methylation [67].…”

Section: Glioblastoma Stem Cells and U87 Glioblastoma Cell Linementioning

confidence: 99%

Insights into the Regulatory Role of m6A Epitranscriptome in Glioblastoma

Galardi

Michienzi

Ciafrè

2020

IJMS

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N6-methyladenosine (m6A) is one of the most widespread and abundant internal messenger RNA modifications found in eukaryotes. Emerging evidence suggests that this modification is strongly linked to the activation and inhibition of cancer pathways and is associated with prognostically significant tumour subtypes. The present review describes the dynamic nature of m6A regulator enzymes, as methyltransferases, demethylases and m6A binding proteins, and points out thevalue of the balance among these proteins in regulating gene expression, cell metabolism and cancer development. The main focus of this review is on the roles of m6A modification in glioblastoma, the most aggressive and invariably lethal brain tumour. Although the study of m6A in glioblastoma is a young one, and papers in this field can yield divergent conclusions, the results collected so far clearly demonstrate that modulation of mRNA m6A levels impacts multiple aspects of this tumour, including growth, glioma stem cells self-renewal, and tumorigenesis, suggesting that mRNA m6A modification may serve as a promising target for glioblastoma therapy. We also present recent data about another type of epitranscriptomic modification, the methylation of cytosine at a specific site of 28S rRNA, as it was recently shown to affect the biology of glioma cells, with high potential of clinical implications.

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Section: Glioblastoma Stem Cells and U87 Glioblastoma Cell Linementioning

confidence: 99%

Insights into the Regulatory Role of m6A Epitranscriptome in Glioblastoma

Galardi

Michienzi

Ciafrè

2020

IJMS

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“…Among them, YTHDF2 is known to promote mRNA decay in the cytoplasm [32,33]. However, in addition to its role in turnover, m 6 A has also been implicated in mRNA processing, export and translation, reviewed in [28], as well as in editing [34]. Thus, m 6 A illustrates what can be expected of RNA modifications more broadly, namely that they might have diverse, contextdependent functions.…”

Section: Introductionmentioning

confidence: 99%

Multiple links between 5-methylcytosine content of mRNA and translation

et al. 2020

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Background: 5-Methylcytosine (m 5 C) is a prevalent base modification in tRNA and rRNA but it also occurs more broadly in the transcriptome, including in mRNA, where it serves incompletely understood molecular functions. In pursuit of potential links of m 5 C with mRNA translation, we performed polysome profiling of human HeLa cell lysates and subjected RNA from resultant fractions to efficient bisulfite conversion followed by RNA sequencing (bsRNA-seq). Bioinformatic filters for rigorous site calling were devised to reduce technical noise.Results: We obtained~1000 candidate m 5 C sites in the wider transcriptome, most of which were found in mRNA. Multiple novel sites were validated by amplicon-specific bsRNA-seq in independent samples of either human HeLa, LNCaP and PrEC cells. Furthermore, RNAi-mediated depletion of either the NSUN2 or TRDMT1 m 5 C:RNA methyltransferases showed a clear dependence on NSUN2 for the majority of tested sites in both mRNAs and noncoding RNAs. Candidate m 5 C sites in mRNAs are enriched in 5′UTRs and near start codons and are embedded in a local context reminiscent of the NSUN2-dependent m 5 C sites found in the variable loop of tRNA. Analysing mRNA sites across the polysome profile revealed that modification levels, at bulk and for many individual sites, were inversely correlated with ribosome association. Conclusions: Our findings emphasise the major role of NSUN2 in placing the m 5 C mark transcriptome-wide. We further present evidence that substantiates a functional interdependence of cytosine methylation level with mRNA translation. Additionally, we identify several compelling candidate sites for future mechanistic analysis.

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“…Among them, YTHDF2 is known to promote mRNA decay in the cytoplasm Du et al 2016). However, in addition to its role in turnover, m 6 A has also been implicated in mRNA processing, export and translation, reviewed in (Zaccara et al 2019), as well as in editing (Xiang et al 2018). Thus, m 6 A illustrates what can be expected of RNA modifications more broadly, namely that they might have diverse, context-dependent functions.…”

Section: Introductionmentioning

confidence: 99%

Multiple links between 5-methylcytosine content of mRNA and translation

Schümann

Zhang²,

Sibbritt

et al. 2020

Preprint

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Abstract5-methylcytosine (m5C) is a prevalent base modification in tRNA and rRNA but it also occurs more broadly in the transcriptome, including in mRNA, where it serves incompletely understood molecular functions. In pursuit of potential links of m5C with mRNA translation, we performed polysome profiling of human HeLa cell lysates and subjected RNA from resultant fractions to efficient bisulfite conversion followed by RNA sequencing (bsRNA-seq). Bioinformatic filters for rigorous site calling were devised to reduce technical noise. We obtained ∼1,000 candidate m5C sites in the wider transcriptome, most of which were found in mRNA. Multiple novel sites were validated by amplicon-specific bsRNA-seq in independent samples of either human HeLa, LNCaP and PrEC cells. Furthermore, RNAi-mediated depletion of either the NSUN2 or TRDMT1 m5C:RNA methyltransferases showed a clear dependence on NSUN2 for the majority of tested sites in both mRNAs and noncoding RNAs. Candidate m5C sites in mRNAs are enriched in 5’UTRs and near start codons, and are commonly embedded in a local context reminiscent of the NSUN2-dependent m5C sites found in the variable loop of tRNA. Analysing mRNA sites across the polysome profile revealed that modification levels, at bulk and for many individual sites, were inversely correlated with ribosome association. Altogether, these findings emphasise the major role of NSUN2 in making this mark transcriptome-wide and further substantiate a functional interdependence of cytosine methylation level with mRNA translation.

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N6-Methyladenosines Modulate A-to-I RNA Editing

Cited by 118 publications

References 41 publications

Insights into the Regulatory Role of m6A Epitranscriptome in Glioblastoma

Insights into the Regulatory Role of m6A Epitranscriptome in Glioblastoma

Multiple links between 5-methylcytosine content of mRNA and translation

Multiple links between 5-methylcytosine content of mRNA and translation

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