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mouse M6a

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
Y Yan, V Narayanan, C Lagenaur
Two homologous cDNAs were previously isolated by expression cloning with a monoclonal antibody that recognized a CNS neuronal membrane protein. Both cDNAs, M6a and M6b, bore significant homology with the major myelin proteolipid protein, PLP/DM20. Our initial studies of M6 gene expression in the adult mouse brain showed that M6a was present in neurons, PLP/DM20 in oligodendrocytes, and M6b in both neurons and glia. This led to the recognition of a novel gene family that included the oligodendrocyte-specific PLP/DM20 gene and the neuronal M6 genes...
July 8, 1996: Journal of Comparative Neurology
J M Greer, R A Sobel, A Sette, S Southwood, M B Lees, V K Kuchroo
To understand and develop strategies to intervene in autoimmune responses to myelin proteolipid protein (PLP), encephalitogenic epitopes must be identified. To expedite the identification of potentially immunogenic and encephalitogenic epitopes of PLP, overlapping synthetic 20-mer PLP peptides covering the whole PLP molecule were screened for their ability to bind to purified mouse I-Ad, I-Ak, and I-As molecules. The peptides that bound to the I-A molecules were tested for their ability to induce immune responses in corresponding inbred mouse strains...
January 1, 1996: Journal of Immunology: Official Journal of the American Association of Immunologists
P Bringmann, R Lührmann
Antibodies specific for N6-methyladenosine (m6A) were elicited in rabbits and used to study the accessibility in intact snRNPs of the m6A residues present in the snRNAs U2, U4 and U6. The antibody quantitatively precipitates snRNPs U2 and U4/U6 from total nucleoplasmic snRNPs U1-U6 isolated from HeLa cells, which demonstrates that the m6A residues of the respective snRNAs are not protected by snRNP proteins in the snRNP particles. While the anti-m6A IgG does not react at all with U5 RNPs lacking m6A, a significant amount of U1 RNPs was co-precipitated despite the fact that U1 RNA does not contain m6A either...
March 23, 1987: FEBS Letters
S S Ghosh, P S Obermiller, T J Kwoh, T R Gingeras
In murine cells expressing the PaeR7 endonuclease and methylase genes, the recognition sites (CTCGAG) of these enzymes can be methylated at the adenine residue by the PaeR7 methylase and at the internal cytosine by the mouse DNA methyltransferase. Using nonadecameric duplex deoxyoligonucleotide substrates, the specificity of the PaeR7 endonuclease for unmethylated, hemi-methylated, and fully methylated N6-methyladenine (m6A) and C5-methylcytosine (m5C) versions of these substrates has been studied. The Km, Kcat, and Ki values for these model substrates have been measured and suggest that fully or hemi-m6A-methylated PaeR7 sites in the murine genome are completely protected...
September 11, 1990: Nucleic Acids Research
A P Rana, M T Tuck
A T7 RNA transcript coding for mouse dihydrofolate reductase (DHFR) was utilized as a substrate for the N6-methyladenosine mRNA methyltransferase isolated from HeLa cell nuclei. This transcript acted as a 3 fold better substrate than either prolactin mRNA or a synthetic RNA substrate which contained multiple methylation consensus sequences. Formation of internal N6-methyladenine (m6A) residues in the DHFR transcript was shown to increase slightly by the absence of a 7-methylguanine-2'-O-methyl cap structure...
August 25, 1990: Nucleic Acids Research
R P Perry, D E Kelley
A kinetic analysis of the labeling of the methylated components of messenger RNA and heterogeneous nuclear RNA in mouse L cells indicates that the 5' terminal cap I structures (m7GpppXmpYp) of mRNA are derived from 5' terminal cap structures of hnRNA. Most of the hnRNA caps are conserved during processing, whereas only a portion of the internal m6A residues in hnRNA are conserved. The cap II structures (m7GpppXmpYmpZp), which constitute the 5' termini of some mRNAs, arise by a "secondary" methylation that occurs after the mRNAs have entered the cytoplasm...
July 1976: Cell
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