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mouse M6a

Chen-Xin Wang, Guan-Shen Cui, Xiuying Liu, Kai Xu, Meng Wang, Xin-Xin Zhang, Li-Yuan Jiang, Ang Li, Ying Yang, Wei-Yi Lai, Bao-Fa Sun, Gui-Bin Jiang, Hai-Lin Wang, Wei-Min Tong, Wei Li, Xiu-Jie Wang, Yun-Gui Yang, Qi Zhou
N6-methyladenosine (m6A) RNA methylation is the most abundant modification on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. However, the in vivo functions of METTL3 and m6A modification in mammalian development remain unclear. Here, we show that specific inactivation of Mettl3 in mouse nervous system causes severe developmental defects in the brain. Mettl3 conditional knockout (cKO) mice manifest cerebellar hypoplasia caused by drastically enhanced apoptosis of newborn cerebellar granule cells (CGCs) in the external granular layer (EGL)...
June 7, 2018: PLoS Biology
Seth D Kasowitz, Jun Ma, Stephen J Anderson, N Adrian Leu, Yang Xu, Brian D Gregory, Richard M Schultz, P Jeremy Wang
The N6-methyladenosine (m6A) modification is the most prevalent internal RNA modification in eukaryotes. The majority of m6A sites are found in the last exon and 3' UTRs. Here we show that the nuclear m6A reader YTHDC1 is essential for embryo viability and germline development in mouse. Specifically, YTHDC1 is required for spermatogonial development in males and for oocyte growth and maturation in females; Ythdc1-deficient oocytes are blocked at the primary follicle stage. Strikingly, loss of YTHDC1 leads to extensive alternative polyadenylation in oocytes, altering 3' UTR length...
May 25, 2018: PLoS Genetics
Shu-Jing Liu, Hui-Ling Tang, Qian He, Ping Lu, Tao Fu, Xu-Ling Xu, Tao Su, Mei-Mei Gao, Shumin Duan, Yan Luo, Yue-Sheng Long
Fat mass and obesity-associated (FTO) protein is a ferrous ion (Fe2+)/2-oxoglutarate (2-OG)-dependent demethylase preferentially catalyzing m6A sites in RNA. The FTO gene is highly expressed in the hypothalamus with fluctuation in response to various nutritional conditions, which is believed to be involved in the control of whole body metabolism. However, the underlying mechanism in response to different nutritional cues remains poorly understood. Here we show that ketogenic diet-derived ketone body β-hydroxybutyrate (BHB) transiently increases FTO expression in both mouse hypothalamus and cultured cells...
May 16, 2018: Journal of Molecular Cell Biology
Ziyu Ma, Yahui Ren, Min Ling, Huayan Wang
In post-transcriptional mRNA modification, m⁶A has been observed in a wide range of eukaryotes. METTL3, as a component of methyltransferase complex for m⁶A modification, regulates mouse naïve pluripotency and influences mRNA stability, especially affecting the expression level of the key pluripotent transcription factors. To reveal the expression pattern of the porcine METTL3 gene, we analyzed METTL3 expression level in different porcine tissues, somatic cells, and induced pluripotent stem cells (piPSCs) by RT-PCR...
March 25, 2018: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Dandan Yang, Jing Qiao, Guiying Wang, Yuanyuan Lan, Guoping Li, Xudong Guo, Jiajie Xi, Dan Ye, Songcheng Zhu, Wen Chen, Wenwen Jia, Ye Leng, Xiaoping Wan, Jiuhong Kang
Previous studies have revealed the critical roles of N6-methyladenosine (m6A) modification of mRNA in embryonic stem cells (ESCs), but the biological function of m6A in large intergenic noncoding RNA (lincRNA) is unknown. Here, we showed that the internal m6A modification of linc1281 mediates a competing endogenous RNA (ceRNA) model to regulate mouse ESC (mESC) differentiation. We demonstrated that loss of linc1281 compromises mESC differentiation and that m6A is highly enriched within linc1281 transcripts...
May 4, 2018: Nucleic Acids Research
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 (m6 A) affects multiple aspects of mRNA metabolism and regulates developmental transitions by promoting mRNA decay. Little is known about the role of m6 A in the adult mammalian nervous system. Here we report that sciatic nerve lesion elevates levels of m6 A-tagged transcripts encoding many regeneration-associated genes and protein translation machinery components in the adult mouse dorsal root ganglion (DRG). Single-base resolution m6 A-CLIP mapping further reveals a dynamic m6 A 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 (m6 A) 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 m6 A 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 m6 A modification enhances NSC self-renewal. Decreases in the NSC pool led to a decreased number of late-born neurons during cortical neurogenesis...
February 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 in a previous study that residues in exons are methylated (m6 A) 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 m6 A content in HeLa cell mRNA, suggesting that specification of mRNA stability may be the major role of m6 A exon modification...
March 2018: 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 (m6 A), 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 m6 A modification in GSC (neurosphere) maintenance and dedifferentiation of glioma cells. METTL3 expression is elevated in GSC and attenuated during differentiation...
January 25, 2018: 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
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