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N-6-methyladenosine RNA

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https://www.readbyqxmd.com/read/29666467/ascorbic-acid-induces-global-epigenetic-reprogramming-to-promote-meiotic-maturation-and-developmental-competence-of-porcine-oocytes
#1
Xiao-Xia Yu, Yun-Hua Liu, Xiao-Man Liu, Pei-Chao Wang, Shuai Liu, Jia-Kun Miao, Zhi-Qiang Du, Cai-Xia Yang
L-ascorbic acid (Vitamin C) can enhance the meiotic maturation and developmental competence of porcine oocytes, but the underlying molecular mechanism remains obscure. Here we show the role of ascorbic acid in regulating epigenetic status of both nucleic acids and chromatin to promote oocyte maturation and development in pigs. Supplementation of 250 μM L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AA2P) during in vitro maturation significantly enhanced the nuclear maturation (as indicated by higher rate of first polar body extrusion and increased Bmp15 mRNA level), reduced level of reactive oxygen species, and promoted developmental potency (higher cleavage and blastocyst rates of parthenotes, and decreased Bax and Caspase3 mRNA levels in blastocysts) of pig oocytes...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29643844/emerging-roles-of-n-6-methyladenosine-on-hiv-1-rna-metabolism-and-viral-replication
#2
REVIEW
Sebastián Riquelme-Barrios, Camila Pereira-Montecinos, Fernando Valiente-Echeverría, Ricardo Soto-Rifo
N6 -methyladenosine (m6 A) is the most abundant internal modification present in Eukaryotic mRNA. The functions of this chemical modification are mediated by m6 A-binding proteins (m6 A readers) and regulated by methyltransferases (m6 A writers) and demethylases (m6 A erasers), which together are proposed to be responsible of a new layer of post-transcriptional control of gene expression. Despite the presence of m6 A in a retroviral genome was reported more than 40 years ago, the recent development of sequencing-based technologies allowing the mapping of m6 A in a transcriptome-wide manner made it possible to identify the topology and dynamics of m6 A during replication of HIV-1 as well as other viruses...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29555755/xio-is-a-component-of-the-drosophila-sex-determination-pathway-and-rna-n-6-methyladenosine-methyltransferase-complex
#3
Jian Guo, Hong-Wen Tang, Jing Li, Norbert Perrimon, Dong Yan
N 6 -methyladenosine (m6 A), the most abundant chemical modification in eukaryotic mRNA, has been implicated in Drosophila sex determination by modifying Sex-lethal ( Sxl ) pre-mRNA and facilitating its alternative splicing. Here, we identify a sex determination gene, CG7358 , and rename it xio according to its loss-of-function female-to-male transformation phenotype. xio encodes a conserved ubiquitous nuclear protein of unknown function. We show that Xio colocalizes and interacts with all previously known m6 A writer complex subunits (METTL3, METTL14, Fl(2)d/WTAP, Vir/KIAA1429, and Nito/Rbm15) and that loss of xio is associated with phenotypes that resemble other m6 A factors, such as sexual transformations, Sxl splicing defect, held-out wings, flightless flies, and reduction of m6 A levels...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29542011/solution-structure-of-the-rna-recognition-domain-of-mettl3-mettl14-n-6-methyladenosine-methyltransferase
#4
Jinbo Huang, Xu Dong, Zhou Gong, Ling-Yun Qin, Shuai Yang, Yue-Ling Zhu, Xiang Wang, Delin Zhang, Tingting Zou, Ping Yin, Chun Tang
N6 -methyladenosine (m6 A), a ubiquitous RNA modification, is installed by METTL3-METTL14 complex. The structure of the heterodimeric complex between the methyltransferase domains (MTDs) of METTL3 and METTL14 has been previously determined. However, the MTDs alone possess no enzymatic activity. Here we present the solution structure for the zinc finger domain (ZFD) of METTL3, the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14. We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3' consensus sequence, but does not to one without...
March 14, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29522904/dual-signal-amplified-photoelectrochemical-biosensor-for-detection-of-n-6-methyladenosine-based-on-bivo-4-110-tio-2-heterojunction-ag-mediated-cytosine-pairs
#5
Haiyan Wang, Huanshun Yin, Hua Huang, Kelin Li, Yunlei Zhou, Geoffrey I N Waterhouse, Hai Lin, Shiyun Ai
Herein, a novel dual-signal amplified photoelectrochemical (PEC) biosensor was successfully developed for the highly selective detection of N6 -methyladenosine (m6 A) methylated RNA. The PEC biosensor comprised BiVO4 -110-TiO2 heterojunction and gold nanoparticle decorated MoS2 (MoS2 -AuNPs) as the photoactive materials, horseradish peroxidase conjugated biotin (HRP-Biotin) as the enzymatic unit, Ag+ -mediated cytosine pairs (C-Ag+ -C) as the signal amplification unit, and the anti-m6 A antibody as the m6 A methylated RNA recognition unit...
February 27, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29507755/virma-mediates-preferential-m-6-a-mrna-methylation-in-3-utr-and-near-stop-codon-and-associates-with-alternative-polyadenylation
#6
Yanan Yue, Jun Liu, Xiaolong Cui, Jie Cao, Guanzheng Luo, Zezhou Zhang, Tao Cheng, Minsong Gao, Xiao Shu, Honghui Ma, Fengqin Wang, Xinxia Wang, Bin Shen, Yizhen Wang, Xinhua Feng, Chuan He, Jianzhao Liu
N 6 -methyladenosine (m6 A) is enriched in 3'untranslated region (3'UTR) and near stop codon of mature polyadenylated mRNAs in mammalian systems and has regulatory roles in eukaryotic mRNA transcriptome switch. Significantly, the mechanism for this modification preference remains unknown, however. Herein we report a characterization of the full m6 A methyltransferase complex in HeLa cells identifying METTL3/METTL14/WTAP/VIRMA/HAKAI/ZC3H13 as the key components, and we show that VIRMA mediates preferential mRNA methylation in 3'UTR and near stop codon...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29488640/curcumin-attenuates-lipopolysaccharide-induced-hepatic-lipid-metabolism-disorder-by-modification-of-m-6-a-rna-methylation-in-piglets
#7
Na Lu, Xingmei Li, Jiayao Yu, Yi Li, Chao Wang, Lili Zhang, Tian Wang, Xiang Zhong
N6 -methyladenosine (m6 A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m6 A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m6 A RNA methylation in weaned piglets. A total of 24 Duroc × Large White × Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200 mg/kg dietary curcumin) groups (n = 8/group)...
January 2018: Lipids
https://www.readbyqxmd.com/read/29476152/recognition-of-rna-n-6-methyladenosine-by-igf2bp-proteins-enhances-mrna-stability-and-translation
#8
Huilin Huang, Hengyou Weng, Wenju Sun, Xi Qin, Hailing Shi, Huizhe Wu, Boxuan Simen Zhao, Ana Mesquita, Chang Liu, Celvie L Yuan, Yueh-Chiang Hu, Stefan Hüttelmaier, Jennifer R Skibbe, Rui Su, Xiaolan Deng, Lei Dong, Miao Sun, Chenying Li, Sigrid Nachtergaele, Yungui Wang, Chao Hu, Kyle Ferchen, Kenneth D Greis, Xi Jiang, Minjie Wei, Lianghu Qu, Jun-Lin Guan, Chuan He, Jianhua Yang, Jianjun Chen
N6 -methyladenosine (m6 A) is the most prevalent modification in eukaryotic messenger RNAs (mRNAs) and is interpreted by its readers, such as YTH domain-containing proteins, to regulate mRNA fate. Here, we report the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; including IGF2BP1/2/3) as a distinct family of m6 A readers that target thousands of mRNA transcripts through recognizing the consensus GG(m6 A)C sequence. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6 A-dependent manner under normal and stress conditions and therefore affect gene expression output...
March 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29218006/reduced-levels-of-the-synaptic-functional-regulator-fmrp-in-dentate-gyrus-of-the-aging-sprague-dawley-rat
#9
Roman Smidak, Fernando J Sialana, Martina Kristofova, Tamara Stojanovic, Dragana Rajcic, Jovana Malikovic, Daniel D Feyissa, Volker Korz, Harald Hoeger, Judit Wackerlig, Diana Mechtcheriakova, Gert Lubec
Fragile X mental retardation protein (FMRP) encoded by Fragile X mental retardation 1 ( FMR1 ) gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the development of Fragile X syndrome (FXS) that is characterized by intellectual disability and other behavioral problems including autism. In the rat FXS model, the lack of FMRP caused a deficit in hippocampal-dependent memory...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29154383/detection-of-n-6-methyladenosine-based-on-the-methyl-sensitivity-of-mazf-rna-endonuclease
#10
Miki Imanishi, Shogo Tsuji, Akiyo Suda, Shiroh Futaki
We found that Escherichia coli MazF toxin, an ACA-sequence-specific endoribonuclease, was sensitive to N6 -methyladenosine (m6A), representing the first m6A-sensitive RNA cleavage enzyme. The methyl-sensitivity of MazF allowed simple analyses of both m6A demethylase and methyltransferase activity. Furthermore, the approach could be used for inhibitor screening.
November 30, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29125941/epitranscriptomics-regulation-of-mrna-metabolism-through-modifications
#11
REVIEW
Eyal Peer, Gideon Rechavi, Dan Dominissini
Cellular RNAs can be modified post-transcriptionally with dynamic and reversible chemical modifications. These modifications can alter the structure and metabolism of mRNA, but only recent methodological and conceptual advances allowed systematic mapping and functional analysis to unfold the role they play in mRNA biology. Mapping the most common internal mRNA modification, N6 -methyladenosine (m6 A), paved the way for the deciphering of other types of mRNA modifications, such as N1 -methyladenosine (m1 A)...
December 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29109479/viral-and-cellular-n-6-methyladenosine-and-n-6-2-o-dimethyladenosine-epitranscriptomes-in-the-kshv-life-cycle
#12
Brandon Tan, Hui Liu, Songyao Zhang, Suzane Ramos da Silva, Lin Zhang, Jia Meng, Xiaodong Cui, Hongfeng Yuan, Océane Sorel, Shao-Wu Zhang, Yufei Huang, Shou-Jiang Gao
N6 -methyladenosine (m6 A) and N6 ,2'-O-dimethyladenosine (m6 Am) modifications (m6 A/m) of messenger RNA mediate diverse cellular functions. Oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) has latent and lytic replication phases that are essential for the development of KSHV-associated cancers. To date, the role of m6 A/m in KSHV replication and tumorigenesis is unclear. Here, we provide mechanistic insights by examining the viral and cellular m6 A/m epitranscriptomes during KSHV latent and lytic infection...
January 2018: Nature Microbiology
https://www.readbyqxmd.com/read/29103884/reading-m-6-a-in-the-transcriptome-m-6-a-binding-proteins
#13
REVIEW
Deepak P Patil, Brian F Pickering, Samie R Jaffrey
N6 -Methyladenosine (m6 A) is the most prevalent post-transcriptional modification of eukaryotic mRNA and long noncoding RNA. m6 A mediates its effects primarily by recruiting proteins, including the multiprotein eukaryotic initiation factor 3 complex and a set of proteins that contain the YTH domain. Here we describe the mechanisms by which YTH domain-containing proteins bind m6 A and influence the fate of m6 A-containing RNA in mammalian cells. We discuss the diverse, and occasionally contradictory, functions ascribed to these proteins and the emerging concepts that are influencing our understanding of these proteins and their effects on the epitranscriptome...
February 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29051200/human-mettl16-is-a-n-6-methyladenosine-m-6-a-methyltransferase-that-targets-pre-mrnas-and-various-non-coding-rnas
#14
Ahmed S Warda, Jens Kretschmer, Philipp Hackert, Christof Lenz, Henning Urlaub, Claudia Höbartner, Katherine E Sloan, Markus T Bohnsack
N 6 -methyladenosine (m6 A) is a highly dynamic RNA modification that has recently emerged as a key regulator of gene expression. While many m6 A modifications are installed by the METTL3-METTL14 complex, others appear to be introduced independently, implying that additional human m6 A methyltransferases remain to be identified. Using crosslinking and analysis of cDNA (CRAC), we reveal that the putative human m6 A "writer" protein METTL16 binds to the U6 snRNA and other ncRNAs as well as numerous lncRNAs and pre-mRNAs...
November 2017: EMBO Reports
https://www.readbyqxmd.com/read/29043484/the-role-of-yeast-m-6-a-methyltransferase-in-peroxisomal-fatty-acid-oxidation
#15
REVIEW
Pradeep Kumar Yadav, Praveen Kumar Rajvanshi, Ram Rajasekharan
The precise and controlled regulation of gene expression at transcriptional and post-transcriptional levels is crucial for the eukaryotic cell survival and functions. In eukaryotes, more than 100 types of post-transcriptional RNA modifications have been identified. The N(6)-methyladenosine (m(6)A) modification in mRNA is among the most common post-transcriptional RNA modifications known in eukaryotic organisms, and the m(6)A RNA modification can regulate gene expression. The role of yeast m(6)A methyltransferase (Ime4) in meiosis, sporulation, triacylglycerol metabolism, vacuolar morphology, and mitochondrial functions has been reported...
October 17, 2017: Current Genetics
https://www.readbyqxmd.com/read/29033321/regulation-of-m-6-a-transcripts-by-the-3-%C3%A2-5-rna-helicase-ythdc2-is-essential-for-a-successful-meiotic-program-in-the-mammalian-germline
#16
Magdalena Natalia Wojtas, Radha Raman Pandey, Mateusz Mendel, David Homolka, Ravi Sachidanandam, Ramesh S Pillai
N(6)-methyladenosine (m(6)A) is an essential internal RNA modification that is critical for gene expression control in most organisms. Proteins with a YTH domain recognize m(6)A marks and are mediators of molecular functions like RNA splicing, mRNA decay, and translation control. Here we demonstrate that YTH domain-containing 2 (YTHDC2) is an m(6)A reader that is essential for male and female fertility in mice. High-throughput mapping of the m(6)A transcriptome and expression analysis in the Yhtdc2 mutant testes reveal an upregulation of m(6)A-enriched transcripts...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28984244/ythdc1-mediates-nuclear-export-of-n-6-methyladenosine-methylated-mrnas
#17
Ian A Roundtree, Guan-Zheng Luo, Zijie Zhang, Xiao Wang, Tao Zhou, Yiquang Cui, Jiahao Sha, Xingxu Huang, Laura Guerrero, Phil Xie, Emily He, Bin Shen, Chuan He
N(6)-methyladenosine (m(6)A) is the most abundant internal modification of eukaryotic messenger RNA (mRNA) and plays critical roles in RNA biology. The function of this modification is mediated by m(6)A-selective 'reader' proteins of the YTH family, which incorporate m(6)A-modified mRNAs into pathways of RNA metabolism. Here, we show that the m(6)A-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells. Knockdown of YTHDC1 results in an extended residence time for nuclear m(6)A-containing mRNA, with an accumulation of transcripts in the nucleus and accompanying depletion within the cytoplasm...
October 6, 2017: ELife
https://www.readbyqxmd.com/read/28975387/the-m-6-a-methyltransferase-ime4-and-mitochondrial-functions-in-yeast
#18
REVIEW
Pradeep Kumar Yadav, Ram Rajasekharan
In eukaryotes, the precise transcriptional and post-transcriptional regulations of gene expression are crucial for the developmental processes. More than 100 types of post-transcriptional RNA modifications have been identified in eukaryotes. The deposition of N(6)-methyladenosine (m(6)A) into mRNA is among the most common post-transcriptional RNA modifications known in eukaryotes. It has been reported that m(6)A RNA modification can regulate gene expression. The role of yeast m(6)A methyltransferase (Ime4) in meiosis and sporulation in diploid cells is very well proven, but its physiological role in haploid cells has remained unknown until recently...
October 3, 2017: Current Genetics
https://www.readbyqxmd.com/read/28945705/thiol-linked-alkylation-of-rna-to-assess-expression-dynamics
#19
Veronika A Herzog, Brian Reichholf, Tobias Neumann, Philipp Rescheneder, Pooja Bhat, Thomas R Burkard, Wiebke Wlotzka, Arndt von Haeseler, Johannes Zuber, Stefan L Ameres
Gene expression profiling by high-throughput sequencing reveals qualitative and quantitative changes in RNA species at steady state but obscures the intracellular dynamics of RNA transcription, processing and decay. We developed thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM seq), an orthogonal-chemistry-based RNA sequencing technology that detects 4-thiouridine (s4 U) incorporation in RNA species at single-nucleotide resolution. In combination with well-established metabolic RNA labeling protocols and coupled to standard, low-input, high-throughput RNA sequencing methods, SLAM seq enabled rapid access to RNA-polymerase-II-dependent gene expression dynamics in the context of total RNA...
December 2017: Nature Methods
https://www.readbyqxmd.com/read/28931651/region-specific-rna-m-6-a-methylation-represents-a-new-layer-of-control-in-the-gene-regulatory-network-in-the-mouse-brain
#20
Mengqi Chang, Hongyi Lv, Weilong Zhang, Chunhui Ma, Xue He, Shunli Zhao, Zhi-Wei Zhang, Yi-Xin Zeng, Shuhui Song, Yamei Niu, Wei-Min Tong
N(6)-methyladenosine (m(6)A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m(6)A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection...
September 2017: Open Biology
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