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mouse M6a

Yi-Lan Weng, Xu Wang, Ran An, Jessica Cassin, Caroline Vissers, Yuanyuan Liu, Yajing Liu, Tianlei Xu, Xinyuan Wang, Samuel Zheng Hao Wong, Jessica Joseph, Louis C Dore, Qiang Dong, Wei Zheng, Peng Jin, Hao Wu, Bin Shen, Xiaoxi Zhuang, Chuan He, Kai Liu, Hongjun Song, Guo-Li Ming
N6-methyladenosine (m6A) affects multiple aspects of mRNA metabolism and regulates developmental transitions by promoting mRNA decay. Little is known about the role of m6A in the adult mammalian nervous system. Here we report that sciatic nerve lesion elevates levels of m6A-tagged transcripts encoding many regeneration-associated genes and protein translation machinery components in the adult mouse dorsal root ganglion (DRG). Single-base resolution m6A-CLIP mapping further reveals a dynamic m6A landscape in the adult DRG upon injury...
January 17, 2018: Neuron
Yang Wang, Yue Li, Minghui Yue, Jun Wang, Sandeep Kumar, Robert J Wechsler-Reya, Zhaolei Zhang, Yuya Ogawa, Manolis Kellis, Gregg Duester, Jing Crystal Zhao
Internal N6-methyladenosine (m6A) modification is widespread in messenger RNAs (mRNAs) and is catalyzed by heterodimers of methyltransferase-like protein 3 (Mettl3) and Mettl14. To understand the role of m6A in development, we deleted Mettl14 in embryonic neural stem cells (NSCs) in a mouse model. Phenotypically, NSCs lacking Mettl14 displayed markedly decreased proliferation and premature differentiation, suggesting that m6A modification enhances NSC self-renewal. Decreases in the NSC pool led to a decreased number of late-born neurons during cortical neurogenesis...
January 15, 2018: Nature Neuroscience
Robert B Darnell, Shengdong Ke, James E Darnell
By using a cell fraction technique that separates chromatin associated nascent RNA, newly completed nucleoplasmic mRNA and cytoplasmic mRNA, we have shown that residues in exons are methylated (m6A) in nascent pre-mRNA and remain methylated in the same exonic residues in nucleoplasmic and cytoplasmic mRNA. Thus, there is no evidence of a substantial degree of demethylation in mRNA exons that would correspond to so-called "epigenetic" demethylation. The turnover rate of mRNA molecules is faster depending on m6A content in HeLa cell mRNA suggesting specification of mRNA stability may be the major role of m6A exon modification...
December 8, 2017: RNA
Nathan C Boles, Sally Temple
Yoon et al. (2017) uncover a key role for the m6A RNA mark in regulating the timing of cerebral cortex development in mouse and human. This discovery opens new avenues of exploration into how the epitranscriptome helps orchestrate central nervous system formation.
November 15, 2017: Neuron
A Visvanathan, V Patil, A Arora, A S Hegde, A Arivazhagan, V Santosh, K Somasundaram
Despite advances in biology and therapeutic modalities, existence of highly tumorigenic glioma stem-like cells (GSCs) makes glioblastomas (GBMs) invincible. N6-methyl adenosine (m6A), one of the abundant mRNA modifications catalyzed by methyltransferase-like 3 and 14 (METTL3/14), influences various events in RNA metabolism. Here, we report the crucial role of METTL3-mediated m6A modification in GSC (neurosphere) maintenance and dedifferentiation of glioma cells. METTL3 expression is elevated in GSC and attenuated during differentiation...
October 9, 2017: Oncogene
Melisa C Monteleone, Silvia C Billi, Marcela A Brocco, Alberto C Frasch
Membrane neuronal glycoprotein M6a is highly expressed in the brain and contributes to neural plasticity promoting neurite growth and spine and synapse formation. We have previously showed that chronic stressors alter hippocampal M6a mRNA levels in rodents and tree shrews. We now show that M6a glycoprotein can be detected in mouse blood. M6a is a transmembrane glycoprotein and, as such, unlikely to be free in blood. Here we demonstrate that, in blood, M6a is transported in extracellular vesicles (EVs). It is also shown that M6a-containing EVs are delivered from cultured primary neurons as well as from M6a-transfected COS-7 cells...
August 29, 2017: Scientific Reports
Atsuko Honda, Yasuyuki Ito, Kazuko Takahashi-Niki, Natsuki Matsushita, Motohiro Nozumi, Hidenori Tabata, Kosei Takeuchi, Michihiro Igarashi
Lipid raft domains, where sphingolipids and cholesterol are enriched, concentrate signaling molecules. To examine how signaling protein complexes are clustered in rafts, we focused on the functions of glycoprotein M6a (GPM6a), which is expressed at a high concentration in developing mouse neurons. Using imaging of lipid rafts, we found that GPM6a congregated in rafts in a GPM6a palmitoylation-dependent manner, thereby contributing to lipid raft clustering. In addition, we found that signaling proteins downstream of GPM6a, such as Rufy3, Rap2, and Tiam2/STEF, accumulated in lipid rafts in a GPM6a-dependent manner and were essential for laminin-dependent polarity during neurite formation in neuronal development...
April 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Shunian Xiang, Ke Liu, Zhangming Yan, Yaou Zhang, Zhirong Sun
N6-Methyladenosine (m6A) is the most common mRNA modification; it occurs in a wide range of taxon and is associated with many key biological processes. High-throughput experiments have identified m6A-peaks and sites across the transcriptome, but studies of m6A sites at the transcriptome-wide scale are limited to a few species and tissue types. Therefore, the computational prediction of mRNA m6A sites has become an important strategy. In this study, we integrated multiple features of mRNA (flanking sequences, local secondary structure information, and relative position information) and trained a SVM classifier to predict m6A sites in mammalian mRNA sequences...
2016: PloS One
Zsuzsanna Bodi, Andrew Bottley, Nathan Archer, Sean T May, Rupert G Fray
Interest in mRNA methylation has exploded in recent years. The sudden interest in a 40 year old discovery was due in part to the finding of FTO's (Fat Mass Obesity) N6-methyl-adenosine (m6A) deaminase activity, thus suggesting a link between obesity-associated diseases and the presence of m6A in mRNA. Another catalyst of the sudden rise in mRNA methylation research was the release of mRNA methylomes for human, mouse and Saccharomyces cerevisiae. However, the molecular function, or functions of this mRNA 'epimark' remain to be discovered...
2015: PloS One
Bastian Linder, Anya V Grozhik, Anthony O Olarerin-George, Cem Meydan, Christopher E Mason, Samie R Jaffrey
N(6)-methyladenosine (m6A) is the most abundant modified base in eukaryotic mRNA and has been linked to diverse effects on mRNA fate. Current mapping approaches localize m6A residues to transcript regions 100-200 nt long but cannot identify precise m6A positions on a transcriptome-wide level. Here we developed m6A individual-nucleotide-resolution cross-linking and immunoprecipitation (miCLIP) and used it to demonstrate that antibodies to m6A can induce specific mutational signatures at m6A residues after ultraviolet light-induced antibody-RNA cross-linking and reverse transcription...
August 2015: Nature Methods
Xiaodong Cui, Jia Meng, Manjeet K Rao, Yidong Chen, Yufei Huang
BACKGROUND: Methylated RNA Immunoprecipatation combined with RNA sequencing (MeRIP-seq) is revolutionizing the de novo study of RNA epigenomics at a higher resolution. However, this new technology poses unique bioinformatics problems that call for novel and sophisticated statistical computational solutions, aiming at identifying and characterizing transcriptome-wide methyltranscriptome. RESULTS: We developed HEP, a Hidden Markov Model (HMM)-based Exome Peak-finding algorithm for predicting transcriptome methylation sites using MeRIP-seq data...
2015: BMC Genomics
Lian Liu, Shao-Wu Zhang, Yu-Chen Zhang, Hui Liu, Lin Zhang, Runsheng Chen, Yufei Huang, Jia Meng
Biochemical modifications to mRNA, especially N6-methyladenosine (m6A) and 5-methylcytosine (m5C), have been recently shown to be associated with crucial biological functions. Despite the intriguing advancements, little is known so far about the dynamic landscape of RNA methylome across different cell types and how the epitranscriptome is regulated at the system level by enzymes, i.e., RNA methyltransferases and demethylases. To investigate this issue, a meta-analysis of m6A MeRIP-Seq datasets collected from 10 different experimental conditions (cell type/tissue or treatment) is performed, and the combinatorial epitranscriptome, which consists of 42 758 m6A sites, is extracted and divided into 3 clusters, in which the methylation sites are likely to be hyper- or hypo-methylated simultaneously (or co-methylated), indicating the sharing of a common methylation regulator...
January 2015: Molecular BioSystems
Yuchang Li, Jiaohong Wang, Kinji Asahina
In many organs, myofibroblasts play a major role in the scarring process in response to injury. In liver fibrogenesis, hepatic stellate cells (HSCs) are thought to transdifferentiate into myofibroblasts, but the origins of both HSCs and myofibroblasts remain elusive. In the developing liver, lung, and intestine, mesothelial cells (MCs) differentiate into specific mesenchymal cell types; however, the contribution of this differentiation to organ injury is unknown. In the present study, using mouse models, conditional cell lineage analysis has demonstrated that MCs expressing Wilms tumor 1 give rise to HSCs and myofibroblasts during liver fibrogenesis...
February 5, 2013: Proceedings of the National Academy of Sciences of the United States of America
Dan Dominissini, Sharon Moshitch-Moshkovitz, Schraga Schwartz, Mali Salmon-Divon, Lior Ungar, Sivan Osenberg, Karen Cesarkas, Jasmine Jacob-Hirsch, Ninette Amariglio, Martin Kupiec, Rotem Sorek, Gideon Rechavi
An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N(6)-methyladenosine (m(6)A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m(6)A modification landscape in a transcriptome-wide manner, using a novel approach, m(6)A-seq, based on antibody-mediated capture and massively parallel sequencing...
April 29, 2012: Nature
Lars Bochmann, Padmini Sarathchandra, Federica Mori, Enrique Lara-Pezzi, Domenico Lazzaro, Nadia Rosenthal
BACKGROUND: The epicardium has key functions during myocardial development, by contributing to the formation of coronary endothelial and smooth muscle cells, cardiac fibroblasts, and potentially cardiomyocytes. The epicardium plays a morphogenetic role by emitting signals to promote and maintain cardiomyocyte proliferation. In a regenerative context, the adult epicardium might comprise a progenitor cell population that can be induced to contribute to cardiac repair. Although some genes involved in epicardial function have been identified, a detailed molecular profile of epicardial gene expression has not been available...
June 28, 2010: PloS One
Jing Zhao, Atsumi Iida, Yasuo Ouchi, Shinya Satoh, Sumiko Watanabe
PURPOSE: Glycoprotein m6a (M6a) is a cell-surface glycoprotein that belongs to the myelin proteolipid protein family. M6a is expressed mainly in the nervous system, and its expression and function in mammalian retina have not been described. Using proteomics analysis of mouse retinal membrane fractions, we identified M6a as a retinal membrane protein that is strongly expressed at embryonic stages. Our aim was to reveal the function of M6a in development of mouse retina in this work. METHODS: Detailed expression pattern of M6a was examined by immunostaining using frozen sections of mouse retina obtained at various developmental stages...
2008: Molecular Vision
Hideo Michibata, Tsuyoshi Okuno, Nae Konishi, Koji Wakimoto, Kiyoshi Kyono, Kan Aoki, Yasushi Kondo, Kazuyuki Takata, Yoshihisa Kitamura, Takashi Taniguchi
Glycoprotein M6A (GPM6A) is known as a transmembrane protein and an abundant cell surface protein on neurons in the central nervous system (CNS). However, the function of GPM6A is still unknown in the differentiation of neurons derived from embryonic stem (ES) cells. To investigate the function of GPM6A, we generated knockdown mouse ES cell lines (D3m-shM6A) using a short hairpin RNA (shRNA) expression vector driven by the U6 small nuclear RNA promoter, which can significantly suppress the expression of mouse GPM6A mRNA...
August 2008: Stem Cells and Development
David Ratel, Jean-Luc Ravanat, Marie-Pierre Charles, Nadine Platet, Lionel Breuillaud, Joël Lunardi, François Berger, Didier Wion
Three methylated bases, 5-methylcytosine, N4-methylcytosine and N6-methyladenine (m6A), can be found in DNA. However, to date, only 5-methylcytosine has been detected in mammalian genomes. To reinvestigate the presence of m6A in mammalian DNA, we used a highly sensitive method capable of detecting one N6-methyldeoxyadenosine per million nucleosides. Our results suggest that the total mouse genome contains, if any, less than 10(3) m6A. Experiments were next performed on PRED28, a putative mammalian N6-DNA methyltransferase...
May 29, 2006: FEBS Letters
M Yoshida, W S Shan, D R Colman
The recent discovery of a proteolipid protein gene family has revealed that its members are in fact widely distributed and are not exclusively associated with myelination. To date, three different gene products, DMalpha/DM-20/PLP, DMbeta/M6a, and DMgamma/M6b, have been isolated from certain primitive fish species, mouse, and human central nervous system (CNS). We cloned Xenopus laevis orthologues of DMbeta/M6a and DMgamma/M6b and investigated the expression patterns of these gene transcripts as well as that of PLP in developing Xenopus CNS...
July 1, 1999: Journal of Neuroscience Research
K L Heilman, R A Leach, M T Tuck
N6-Methyladenosine (m6A) is found internally in a number of mRNA molecules from higher eucaryotic cells. In these investigations, it was found that the presence of m6A residues increase the in vitro translation efficiency of capped T7 transcripts of mouse dihydrofolate reductase (DHFR) mRNA. Using an in vitro rabbit reticulocyte translation system, the formation of internal m6A residues in the DHFR transcripts resulted in a 1.5-fold increase in translated DHFR compared to transcripts void of internal m6A residues...
July 1996: International Journal of Biochemistry & Cell Biology
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