Landscape and Regulation of m6A and m6Am Methylome across Human and Mouse Tissues

Liu, Jun’e; Li, Kai; Cai, Jia‐Bin; Zhang, Mingchang; Zhang, Xiaoting; Xiong, Xushen; Meng, Haowei; Xu, Xizhan; Huang, Zhibin; Ji, Peng; Fan, Jian‐Gao

doi:10.1016/j.molcel.2019.09.032

Cited by 214 publications

(195 citation statements)

References 74 publications

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“…It will be interesting to compare the expression profiles of these enzymes in different plant species. Indeed, Liu et al (2020) profiled m 6 A and N 6 ,2’-O-dimethyladenosine (m 6 Am) across human and mouse tissues and suggested that the difference in these epitranscriptomic marks is greater between species than tissue types.…”

Section: Discussionmentioning

confidence: 99%

Time-resolved transcriptome of barley anthers and meiocytes reveals robust and largely stable gene expression changes at meiosis entry

Barakate

Orr

Schreiber

et al. 2020

Preprint

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In flowering plants, successful germinal cell development and meiotic recombination depend upon a combination of environmental and genetic factors. To gain insights into this specialised reproductive development programme we used short- and long-read RNA-sequencing (RNA-seq) to study the temporal dynamics of transcript abundance in immuno-cytologically staged barley (Hordeum vulgare) anthers and meiocytes. We show that the most significant transcriptional changes occur at the transition from pre-meiosis to leptotene–zygotene, which is followed by largely stable transcript abundance throughout prophase I. Our analysis reveals that the developing anthers and meiocytes are enriched in long non-coding RNAs (lncRNAs) and that entry to meiosis is characterized by their robust and significant down regulation. Intriguingly, only 24% of a collection of putative meiotic gene orthologues showed differential transcript abundance in at least one stage or tissue comparison. Changes in the abundance of numerous transcription factors, representatives of the small RNA processing machinery, and post-translational modification pathways highlight the complexity of the regulatory networks involved. These developmental, time-resolved, and dynamic transcriptomes increase our understanding of anther and meiocyte development and will help guide future research.One sentence summaryAnalysis of RNA-seq data from meiotically staged barley anthers and meiocytes highlights the role of lncRNAs within a complex network of transcriptional and post-transcriptional regulation accompanied by a hiatus in differential gene expression during prophase I.The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Robbie Waugh (robbie.waugh@hutton.ac.uk)

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Section: Discussionmentioning

confidence: 99%

Time-resolved transcriptome of barley anthers and meiocytes reveals robust and largely stable gene expression changes at meiosis entry

Barakate

Orr

Schreiber

et al. 2020

Preprint

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“…Another report has described that m6A modifications by the tRNA methyltransferase, NSun2, suppress the miRNA processing of miR-125 [84]. In addition, m6A modifications are enriched at the 3 UTRs and miRNA target sites of mRNAs, and miRNAs are reported to regulate m6A abundance by modulating METTL3 binding to mRNAs [85,86]. In contrast, phospho-dimethylation of the 5 ends of pre-miRNAs by the RNA methyltransferase, BCDIN3D, reportedly inhibits Dicer processing [87].…”

Section: Regulation Of Mirnas By Rna Modifications (Epitranscriptomics)mentioning

confidence: 99%

Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis

Matsuyama

Suzuki

2019

IJMS

194

141

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MicroRNAs (miRNAs) are approximately 22-nucleotide-long, small non-coding RNAs that post-transcriptionally regulate gene expression. The biogenesis of miRNAs involves multiple steps, including the transcription of primary miRNAs (pri-miRNAs), nuclear Drosha-mediated processing, cytoplasmic Dicer-mediated processing, and loading onto Argonaute (Ago) proteins. Further, miRNAs control diverse biological and pathological processes via the silencing of target mRNAs. This review summarizes recent findings regarding the quantitative aspects of miRNA homeostasis, including Drosha-mediated pri-miRNA processing, Ago-mediated asymmetric miRNA strand selection, and modifications of miRNA pathway components, as well as the roles of RNA modifications (epitranscriptomics), epigenetics, transcription factor circuits, and super-enhancers in miRNA regulation. These recent advances have facilitated a system-level understanding of miRNA networks, as well as the improvement of RNAi performance for both gene-specific targeting and genome-wide screening. The comprehensive understanding and modeling of miRNA biogenesis and function have been applied to the design of synthetic gene circuits. In addition, the relationships between miRNA genes and super-enhancers provide the molecular basis for the highly biased cell type-specific expression patterns of miRNAs and the evolution of miRNA–target connections, while highlighting the importance of alterations of super-enhancer-associated miRNAs in a variety of human diseases.

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“…RNA m 6 A modification is the most prevalent and abundant modifications that occur in the mRNAs, rRNAs and small nuclear RNAs (snRNAs) [35]. m 6 A modification of mRNA usually occurs in nuclear speckles where the methyltransferases and demethylases are concentrated [29] and are enriched in single nucleotide polymorphisms (SNPs) [36]. 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.…”

Section: Rna M 6 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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Landscape and Regulation of m6A and m6Am Methylome across Human and Mouse Tissues

Abstract: Highlights d m 6 A and m 6 Am methylomes of brain tissues are highly specific d m 6 A and m 6 Am are partially correlated with their writers and erasers d SNPs are enriched in m 6 A-containing regions d Species rather than tissue type is the primary determinant of methylome

Cited by 214 publications

References 74 publications

Time-resolved transcriptome of barley anthers and meiocytes reveals robust and largely stable gene expression changes at meiosis entry

Time-resolved transcriptome of barley anthers and meiocytes reveals robust and largely stable gene expression changes at meiosis entry

Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis

The Emerging Roles of RNA Modifications in Glioblastoma

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