The m<sup>6</sup>A Writer: Rise of a Machine for Growing Tasks

Balacco, Dario Leonardo; Soller, Matthias

doi:10.1021/acs.biochem.8b01166

Cited by 123 publications

(160 citation statements)

References 162 publications

(660 reference statements)

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“…Generally, the enzymatic core METTLE3 and methyltransferase like 14 (METTL14), as well as Wilms' tumor 1-associated protein (WTAP), Virilizer like m6A methyltransferase associated protein (VIRMA/KIAA1429), RNA-binding motif protein 15 (RBM15), RNA-binding motif protein 15B (RBM15B/OTT3), zinc finger CCCH domain-containing protein 13 (ZC3H13, as known as Flacc and KIAA0853) and Hakai (also known as Cbl proto-oncogene like 1, CBLL1) constitute of a methyltransferase complex, also known as m 6 A-METTL associated complex (MACOM), that can mediates the m 6 A methylation. Meanwhile, two demethylases, Fat mass and obesity-associated protein (FTO) and ALKBH5, catalyze the m 6 A demethylation [37][38][39][40][41][42].…”

Section: Rna M 6 a Modification In Gbmmentioning

confidence: 99%

The Emerging Roles of RNA Modifications in Glioblastoma

Dong

Cui

2020

Cancers

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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 6 a Modification In Gbmmentioning

confidence: 99%

The Emerging Roles of RNA Modifications in Glioblastoma

Dong

Cui

2020

Cancers

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“…Many of these factors are also conserved and include the following proteins, denoted with plant name first and mammalian homolog following a slash (see Figs. 1 and 2 for additional details): the splicing factor FKBP12 Interacting Protein37 (FIP37/WTAP; Vespa et al, 2004;Zhong et al, 2008;Liu et al, 2014;Ping et al, 2014;Schwartz et al, 2014b;Shen et al, 2016;R u zička et al, 2017); the protein VIRILIZER (VIR/KIAA1429), originally identified in Drosophila melanogaster (Niessen et al, 2001;Ortega et al, 2003;Schwartz et al, 2014b;R u zička et al, 2017); the putative ubiquitin E3 ligase HAKAI/CBLL1 (Horiuchi et al, 2013;R u zička et al, 2017); the Zn finger protein ZC3H13 (Guo et al, 2018;Knuckles et al, 2018;Wen et al, 2018) without orthologs in plants (Balacco and Soller, 2019); and the RNAbinding proteins RBM15A/B (Horiuchi et al, 2013;Yan and Perrimon, 2015;Lence et al, 2016;Patil et al, 2016). Interestingly, the closest plant homolog of RBM15A/B is FLOWERING LOCUS PA (FPA), an RNA-binding protein required for the control of flowering time (Schomburg et al, 2001).…”

Section: Occurrence Of M 6 a In Plant Transcriptomesmentioning

confidence: 99%

“…YTHDC2 is specific to mammals and contains several other folded domains in addition to the YTHDC domain (Bailey et al, 2017;Wojtas et al, 2017;Kretschmer et al, 2018), while YTHDC1 has long N-and C-terminal IDRs (Patil et al, 2016). YTHDF-and YTHDC1-type proteins are found in many eukaryotes (Balacco and Soller, 2019), including plants, whose genomes encode more YTH domain proteins than other organisms (Li et al, 2014a;Scutenaire et al, 2018). For example, 13 YTH domain-containing proteins are encoded in Arabidopsis (Fig.…”

Section: Reading M 6 Amentioning

confidence: 99%

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Occurrence and Functions of m⁶A and Other Covalent Modifications in Plant mRNA

Arribas-Hernández

Brodersen

2019

Plant Physiol.

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Posttranscriptional control of gene expression is indispensable for the execution of developmental programs and environmental adaptation. Among the many cellular mechanisms that regulate mRNA fate, covalent nucleotide modification has emerged as a major way of controlling the processing, localization, stability, and translatability of mRNAs. This powerful mechanism is conserved across eukaryotes and controls the cellular events that lead to development and growth. As in other eukaryotes, N 6methylation of adenosine is the most abundant and best studied mRNA modification in flowering plants. It is essential for embryonic and postembryonic plant development and it affects growth rate and stress responses, including susceptibility to plant RNA viruses. Although the mRNA modification field is young, the intense interest triggered by its involvement in stem cell differentiation and cancer has led to rapid advances in understanding how mRNA modifications control gene expression in mammalian systems. An equivalent effort from plant molecular biologists has been lagging behind, but recent work in Arabidopsis (Arabidopsis thaliana) and other plant species is starting to give insights into how this essential layer of posttranscriptional regulation works in plants, and both similarities and differences with other eukaryotes are emerging. In this Update, we summarize, connect, and evaluate the experimental work that supports our current knowledge of the biochemistry, molecular mechanisms, and biological functions of mRNA modifications in plants. We devote particular attention to N 6 -methylation of adenosine and attempt to place the knowledge gained from plant studies within the context of a more general framework derived from studies in other eukaryotes.

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“…Methylation at the N6 position in adenosine (m 6 A) is the most common internal modification in 38 eukaryotic mRNA. A methyltransferase complex composed of METTL3, METTL14, WTAP, VIRMA, and 39 other cofactors catalyzes methylation at DRACH/DRAC motifs, primarily in the last exon (1,2). Most m 6 A 40 methylation occurs during transcription (3).…”

Section: Introduction 37mentioning

confidence: 99%

Limits in the detection of m⁶A changes using MeRIP/m⁶A-seq

McIntyre

Gokhale

Cerchietti

et al. 2019

Preprint

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AbstractMany cellular mRNAs contain the modified base m6A, and recent studies have suggested that various stimuli can lead to changes in m6A. The most common method to map m6A and to predict changes in m6A between conditions is methylated RNA immunoprecipitation sequencing (MeRIP-seq), through which methylated regions are detected as peaks in transcript coverage from immunoprecipitated RNA relative to input RNA. Here, we generated replicate controls and reanalyzed published MeRIP-seq data to estimate reproducibility across experiments. We found that m6A peak overlap in mRNAs varies from ∼30 to 60% between studies, even in the same cell type. We then assessed statistical methods to detect changes in m6A peaks as distinct from changes in gene expression. However, from these published data sets, we detected few changes under most conditions and were unable to detect consistent changes across studies of similar stimuli. Overall, our work identifies limits to MeRIP-seq reproducibility in the detection both of peaks and of peak changes and proposes improved approaches for analysis of peak changes.

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The m⁶A Writer: Rise of a Machine for Growing Tasks

Cited by 123 publications

References 162 publications

The Emerging Roles of RNA Modifications in Glioblastoma

The Emerging Roles of RNA Modifications in Glioblastoma

Occurrence and Functions of m⁶A and Other Covalent Modifications in Plant mRNA

Limits in the detection of m⁶A changes using MeRIP/m⁶A-seq

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The m6A Writer: Rise of a Machine for Growing Tasks

Cited by 123 publications

References 162 publications

The Emerging Roles of RNA Modifications in Glioblastoma

The Emerging Roles of RNA Modifications in Glioblastoma

Occurrence and Functions of m6A and Other Covalent Modifications in Plant mRNA

Limits in the detection of m6A changes using MeRIP/m6A-seq

Contact Info

Product

Resources

About

The m⁶A Writer: Rise of a Machine for Growing Tasks

Occurrence and Functions of m⁶A and Other Covalent Modifications in Plant mRNA

Limits in the detection of m⁶A changes using MeRIP/m⁶A-seq