Landscape and Regulation of M &lt;sup&gt;6&lt;/sup&gt;A and M &lt;sup&gt;6&lt;/sup&gt;Am Methylome Across Human and Mouse Tissues

Liu, June; Li, Kai; Cai, Jia‐Bin; Zhang, Mingchang; Zhang, Xiaoting; Xiong, Xushen; Meng, Haowei; Xu, Xizhan; Huang, Zhibin; Fan, Jian‐Gao; Yi, Chengqi

doi:10.2139/ssrn.3397113

Cited by 25 publications

(43 citation statements)

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“…Across human tissues, the global m6A profiles are highly specific in brain tissues and show modest tissue specificity in non-brain tissues. Nevertheless, a subset of tissue-specific m6A sites is sufficient to distinguish different tissue types [35].…”

Section: Reversible M6a Modificationmentioning

confidence: 99%

“…Moreover, YTHDF2 also recruits the CCR4-NOT deadenylation machinery to promote mRNA degradation [44]. On the other hand, 5′ UTR m6A has been suggested to enhance mRNA translation efficiency in a cap-independent manner through YTHDF1 [35]. YTHDF1 binding promotes protein translation of m6Amodified mRNA by recruiting the eIF3 translation initiation complex.…”

Section: M6a Writer Erasers and Readersmentioning

confidence: 99%

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The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

2020

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Liver cancer is a common cancer worldwide. Although the etiological factors of liver carcinogenesis are well defined, the underlying molecular mechanisms remain largely elusive. Epigenetic deregulations, such as aberrant DNA methylation and histone modifications, play a critical role in liver carcinogenesis. Analogous to DNA and core histone proteins, reversible chemical modifications on mRNA have recently been recognized as important regulatory mechanisms to control gene expression. N6-methyladenosine (m6A) is the most prevalent internal mRNA modification in mammalian cells. m6A modification is important for controlling many cellular and biological processes. Deregulation of m6A modification has been recently implicated in human carcinogenesis, including liver cancer. In this review, we summarize the recent findings on m6A regulation and its biological impacts in normal and cancer cells. We will focus on the deregulation of m6A modification and m6A regulators in liver diseases and liver cancers. We will highlight the clinical relevance of m6A deregulation in liver cancer. We will also discuss the potential of exploiting m6A modification for cancer diagnosis and therapeutics.

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Section: Reversible M6a Modificationmentioning

confidence: 99%

Section: M6a Writer Erasers and Readersmentioning

confidence: 99%

The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

2020

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“…Given that m 6 A mapping efforts documented thousands of modified transcripts and 10,000s of individual methylated sites across development, cell types, tissues, environmental perturbations, and diverse disease states (Liu et al, 2020;Roundtree et al, 2017a;Xiao et al, 2019;Zaccara et al, 2019), one might imagine profound phenotypic consequences to knockouts of core m 6 A pathway members. There are indeed phenotypes, but in many respects they are subtler compared to many developmental pathway mutants or other core gene regulatory factors.…”

Section: Introductionmentioning

confidence: 99%

A neural m⁶A/YTHDF pathway is required for learning and memory inDrosophila

Kan

Ott

Joseph

et al. 2020

Preprint

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The roles of epitranscriptomic modifications in mRNA regulation have recently received substantial attention, with appreciation growing for their phenotypically selective impacts within the animal. We adopted Drosophila melanogaster as a model system to study m 6 A, the most abundant internal modification of mRNA. Here, we report proteomic and functional analyses of fly m 6 A-binding proteins, confirming nuclear (YTHDC) and cytoplasmic (YTHDF) YTH domain proteins as the major m 6 A binders. Since all core m 6 A pathway mutants are viable, we assessed in vivo requirements of the m 6 A pathway in cognitive processes. Assays of short term memory revealed an age-dependent requirement of m 6 A writers working via YTHDF, but not YTHDC, comprising the first phenotypes assigned to Drosophila mutants of the cytoplasmic m 6 A reader.These factors promote memory via neural-autonomous activities, and are required in the mushroom body, the center for associative learning. To inform their basis, we mapped m 6 A from wild-type and mettl3 null mutant heads, allowing robust discrimination of Mettl3-dependent m 6 A sites. In contrast to mammalian m 6 A, which is predominant in 3' UTRs, Drosophila m 6 A is highly enriched in 5' UTRs and occurs in an adenosine-rich context. Genomic analyses demonstrate that Drosophila m 6 A does not directionally affect RNA stability, but is preferentially deposited on genes with low translational efficiency. However, functional tests indicate a role for m 6 A in translational activation, since we observe reduced nascent protein synthesis in mettl3-KO cells.Finally, we show that ectopic YTHDF can increase m 6 A target reporter output in an m 6 A-binding dependent manner, and that this activity is required for in vivo neural function of YTHDF in memory. Altogether, we provide the first tissue-specific m 6 A maps in this model organism and reveal selective behavioral and translational defects for m 6 A/YTHDF mutants.

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“…2A), hence is a reversible modification. Dynamic m 6 A methylomes have been identified in physiological processes, across tissues, and in response to stimuli (Dominissini et al, 2012;Meyer et al, 2012;Schwartz et al, 2013;Zhou et al, 2015;Cao and Li, 2016;Roundtree et al, 2017;Liu et al, 2019c;Xiao et al, 2019). As an important epitranscriptomic mark, m 6 A plays critical roles in mRNA splicing, polyadenylation, export, translation, stability, structure, etc.…”

Section: The Biogenesis and Sequencing Approaches For Rna Modificationsmentioning

confidence: 99%

Mapping the epigenetic modifications of DNA and RNA

et al. 2020

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Over 17 and 160 types of chemical modifications have been identified in DNA and RNA, respectively. The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics. Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study. Here, we review the recent technological advances in this rapidly evolving field. We focus on high-throughput detection methods and biological findings for these modifications, and discuss questions to be addressed as well. We also summarize third-generation sequencing methods, which enable long-read and single-molecule sequencing of DNA and RNA modification.

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Landscape and Regulation of M <sup>6</sup>A and M <sup>6</sup>Am Methylome Across Human and Mouse Tissues

Cited by 25 publications

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The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

A neural m⁶A/YTHDF pathway is required for learning and memory inDrosophila

Mapping the epigenetic modifications of DNA and RNA

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Landscape and Regulation of M <sup>6</sup>A and M <sup>6</sup>Am Methylome Across Human and Mouse Tissues

Cited by 25 publications

References 0 publications

The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

A neural m6A/YTHDF pathway is required for learning and memory inDrosophila

Mapping the epigenetic modifications of DNA and RNA

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A neural m⁶A/YTHDF pathway is required for learning and memory inDrosophila