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N-6-methyladenosine RNA

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https://www.readbyqxmd.com/read/28533023/the-rna-modification-n-6-methyladenosine-and-its-implications-in-human-disease
#1
REVIEW
Pedro J Batista
Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community...
May 19, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28499622/m-6-a-in-mrna-an-ancient-mechanism-for-fine-tuning-gene-expression
#2
REVIEW
Jean-Yves Roignant, Matthias Soller
Modifications in mRNA constitute ancient mechanisms to regulate gene expression post-transcriptionally. N(6)-methyladenosine (m(6)A) is the most prominent mRNA modification, and is installed by a large methyltransferase complex (the m(6)A 'writer'), not only specifically bound by RNA-binding proteins (the m(6)A 'readers'), but also removed by demethylases (the m(6)A 'erasers'). m(6)A mRNA modifications have been linked to regulation at multiple steps in mRNA processing. In analogy to the regulation of gene expression by miRNAs, we propose that the main function of m(6)A is post-transcriptional fine-tuning of gene expression...
June 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28454774/identification-of-n-6-methyladenosine-reader-proteins
#3
Katherine I Zhou, Nian Liu, Tao Pan
The reversible N(6)-methyladenosine (m(6)A) modification of eukaryotic messenger RNAs (mRNAs) is a widespread regulatory mechanism that impacts every step in the mRNA life cycle. The effect of m(6)A on mRNA fate depends on the binding of "m(6)A reader" proteins - RNA binding proteins that specifically bind to RNAs containing m(6)A. Here, we describe an RNA pull-down method that can be used to identify novel m(6)A reader proteins starting from a known m(6)A-modified site in cellular or viral RNA. We further describe how a combination of immunoprecipitation-based sequencing methods can be used to identify m(6)A-modified sites bound by an m(6)A reader protein on a transcriptome-wide level...
April 26, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28454518/transcriptome-wide-n-6-methyladenosine-methylome-profiling-of-porcine-muscle-and-adipose-tissues-reveals-a-potential-mechanism-for-transcriptional-regulation-and-differential-methylation-pattern
#4
Xuelian Tao, Jianning Chen, Yanzhi Jiang, Yingying Wei, Yan Chen, Huaming Xu, Li Zhu, Guoqing Tang, Mingzhou Li, Anan Jiang, Surong Shuai, Lin Bai, Haifeng Liu, Jideng Ma, Long Jin, Anxiang Wen, Qin Wang, Guangxiang Zhu, Meng Xie, Jiayun Wu, Tao He, Chunyu Huang, Xiang Gao, Xuewei Li
BACKGROUND: N (6) -methyladenosine (m(6)A) is the most prevalent internal form of modification in messenger RNA in higher eukaryotes and potential regulatory functions of reversible m(6)A methylation on mRNA have been revealed by mapping of m(6)A methylomes in several species. m(6)A modification in active gene regulation manifests itself as altered methylation profiles in a tissue-specific manner or in response to changing cellular or species living environment. However, up to date, there has no data on m(6)A porcine transcriptome-wide map and its potential biological roles in adipose deposition and muscle growth...
April 28, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28440291/identifying-n-6-methyladenosine-sites-using-multi-interval-nucleotide-pair-position-specificity-and-support-vector-machine
#5
Pengwei Xing, Ran Su, Fei Guo, Leyi Wei
N6-methyladenosine (m(6)A) refers to methylation of the adenosine nucleotide acid at the nitrogen-6 position. It plays an important role in a series of biological processes, such as splicing events, mRNA exporting, nascent mRNA synthesis, nuclear translocation and translation process. Numerous experiments have been done to successfully characterize m(6)A sites within sequences since high-resolution mapping of m(6)A sites was established. However, as the explosive growth of genomic sequences, using experimental methods to identify m(6)A sites are time-consuming and expensive...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28433859/photoelectrochemical-immunosensor-for-methylated-rna-detection-based-on-g-c3n4-cds-quantum-dots-heterojunction-and-phos-tag-biotin
#6
Haiyan Wang, Qihai Zhang, Huanshun Yin, Minghui Wang, Wenjing Jiang, Shiyun Ai
N(6)-methyladenosine (m(6)A) is an enigmatic and abundant internal modification in eukaryotic messenger RNA (mRNA), which could affect various aspects of RNA metabolism and mRNA translation. Herein, a novel photoelectrochemical (PEC) immunosensor was constructed for m(6)A detection based on the inhibition of Cu(2+) to the photoactivity of g-C3N4/CdS quantum dots (g-C3N4/CdS) heterojunction, where g-C3N4/CdS heterojunction was used as photoactive material, anti-m(6)A antibody as recognition unit for m(6)A-containing RNA, Phos-tag-biotin as link unit and avidin functionalized CuO as PEC signal indicator...
September 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28399407/messenger-rna-methylation-regulates-glioblastoma-tumorigenesis
#7
Deobrat Dixit, Qi Xie, Jeremy N Rich, Jing Crystal Zhao
Messenger RNA (mRNA) modification provides an additional layer of gene regulation in cells. In this issue of Cancer Cell, Zhang et al. report that ALKBH5, a demethylase of the mRNA modification N(6)-methyladenosine, regulates proliferation and self-renewal of glioblastoma stem-like cells by modulating pre-mRNA stability and expression of the FOXM1 gene.
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28353398/a-fly-view-on-the-roles-and-mechanisms-of-the-m-6-a-mrna-modification-and-its-players
#8
Tina Lence, Matthias Soller, Jean-Yves Roignant
RNA modifications are an emerging layer of posttranscriptional gene regulation in eukaryotes. N(6)-methyladenosine (m(6)A) is among the most abundant modifications in mRNAs (mRNAs) that was shown to influence many physiological processes from yeast to mammals. Like DNA methylation, m(6)A in mRNA is dynamically regulated. A conserved methyltransferase complex catalyzes the deposition of the methyl group on adenosine, which can be removed by specific classes of demethylases. Furthermore, YTH-domain containing proteins can recognize this modification to mediate m(6)A-dependent activities...
March 29, 2017: RNA Biology
https://www.readbyqxmd.com/read/28349455/detection-and-quantification-of-n-6-methyladenosine-in-messenger-rna-by-tlc
#9
Zsuzsanna Bodi, Rupert G Fray
The base-modified nucleotide, N (6)-methyladenosine, is a relatively abundant modification found in the mRNA of most higher eukaryotes. Methylation levels can change dependent upon environmental conditions, cell differentiation state, or following knockdown of members of the methylase complex, and it is often useful to directly measure and compare N (6)-methyladenosine levels between samples. Two dimensional chromatography of radiolabeled nucleotides, following specific nuclease treatments, provides a robust, sensitive, and reproducible assay for this modification...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28349454/mapping-m-6-a-at-individual-nucleotide-resolution-using-crosslinking-and-immunoprecipitation-miclip
#10
Anya V Grozhik, Bastian Linder, Anthony O Olarerin-George, 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 m6A mapping approaches localize m6A residues to 100-200 nt-long regions of transcripts. The precise position of m6A in mRNAs cannot be identified on a transcriptome-wide level because there are no chemical methods to distinguish between m6A and adenosine. Here, we describe a method for using anti-m6A antibodies to induce specific mutational signatures at m6A residues after ultraviolet light-induced antibody-RNA crosslinking and reverse transcription...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28349453/genome-wide-location-analyses-of-n6-methyladenosine-modifications-m-6-a-seq
#11
Benoit Molinie, Cosmas C Giallourakis
N(6)-methyladenosine-sequencing (m(6)A-seq) is a critical tool to obtain an unbiased genome-wide picture of m(6)A sites of modification at high resolution. It allows the study of the impact of various perturbations on m(6)A modification distribution and the study of m(6)A functions. Herein, we describe the m(6)A-seq protocol, which entails RNA immunoprecipitation (RIP) performed on fragmented poly(A) RNA utilizing anti-m(6)A antibodies. The captured/enriched m(6)A positive RNA fragments are subsequently sequenced by RNA-seq in parallel with background control non-immunoprecipitated input RNA fragments...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28349452/liquid-chromatography-mass-spectrometry-for-analysis-of-rna-adenosine-methylation
#12
Bi-Feng Yuan
Dynamic RNA modifications recently were considered to constitute another realm for biological regulation in the form of "RNA epigenetics". N (6)-methyladenosine (m(6)A), one of the most important modifications on RNA, plays a fundamental role in epigenetic regulation of the mammalian transcriptome. We recently established various liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS)-based methods for the sensitive and accurate determination of modified nucleosides in both DNA and RNA...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28344040/m-6-a-demethylase-alkbh5-maintains-tumorigenicity-of-glioblastoma-stem-like-cells-by-sustaining-foxm1-expression-and-cell-proliferation-program
#13
Sicong Zhang, Boxuan Simen Zhao, Aidong Zhou, Kangyu Lin, Shaoping Zheng, Zhike Lu, Yaohui Chen, Erik P Sulman, Keping Xie, Oliver Bögler, Sadhan Majumder, Chuan He, Suyun Huang
The dynamic and reversible N(6)-methyladenosine (m(6)A) RNA modification installed and erased by N(6)-methyltransferases and demethylases regulates gene expression and cell fate. We show that the m(6)A demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs. Integrated transcriptome and m(6)A-seq analyses revealed altered expression of certain ALKBH5 target genes, including the transcription factor FOXM1. ALKBH5 demethylates FOXM1 nascent transcripts, leading to enhanced FOXM1 expression...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28297667/m-6-a-rna-methylation-regulates-the-self-renewal-and-tumorigenesis-of-glioblastoma-stem-cells
#14
Qi Cui, Hailing Shi, Peng Ye, Li Li, Qiuhao Qu, Guoqiang Sun, Guihua Sun, Zhike Lu, Yue Huang, Cai-Guang Yang, Arthur D Riggs, Chuan He, Yanhong Shi
RNA modifications play critical roles in important biological processes. However, the functions of N(6)-methyladenosine (m(6)A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m(6)A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase complex, dramatically promotes human GSC growth, self-renewal, and tumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNA demethylase FTO suppresses GSC growth and self-renewal...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28281539/extensive-translation-of-circular-rnas-driven-by-n-6-methyladenosine
#15
Yun Yang, Xiaojuan Fan, Miaowei Mao, Xiaowei Song, Ping Wu, Yang Zhang, Yongfeng Jin, Yi Yang, Lingling Chen, Yang Wang, Catherine Cl Wong, Xinshu Xiao, Zefeng Wang
Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N(6)-methyladenosine (m(6)A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m(6)A motifs are enriched in circRNAs and a single m(6)A site is sufficient to drive translation initiation. This m(6)A-driven translation requires initiation factor eIF4G2 and m(6)A reader YTHDF3, and is enhanced by methyltransferase METTL3/14, inhibited by demethylase FTO, and upregulated upon heat shock...
March 10, 2017: Cell Research
https://www.readbyqxmd.com/read/28256005/regulatory-role-of-n-6-methyladenosine-m-6-a-methylation-in-rna-processing-and-human-diseases
#16
Wenqiang Wei, Xinying Ji, Xiangqian Guo, Shaoping Ji
N(6) -methyladenosine (m(6) A) modification is an abundant and conservative RNA modification in bacterial and eukaryotic cells. m(6) A modification mainly occurs in the 3' untranslated regions (UTRs) and near the stop codons of mRNA. Diverse strategies have been developed for identifying m(6) A sites in single nucleotide resolution. Dynamic regulation of m(6) A is found in metabolism, embryogenesis and developmental processes, indicating a possible epigenetic regulation role along RNA processing and exerting biological functions...
March 3, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28192787/m-6-a-dependent-maternal-mrna-clearance-facilitates-zebrafish-maternal-to-zygotic-transition
#17
Boxuan Simen Zhao, Xiao Wang, Alana V Beadell, Zhike Lu, Hailing Shi, Adam Kuuspalu, Robert K Ho, Chuan He
The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N(6)-methyladenosine (m(6)A) modified, and the clearance of these maternal mRNAs is facilitated by an m(6)A-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of m(6)A-modified maternal mRNAs and impedes zygotic genome activation...
February 23, 2017: Nature
https://www.readbyqxmd.com/read/28138061/pseudouridine-and-n-6-methyladenosine-modifications-weaken-puf-protein-rna-interactions
#18
Pavanapuresan P Vaidyanathan, Ishraq AlSadhan, Dawn K Merriman, Hashim M Al-Hashimi, Daniel Herschlag
RNA modifications are ubiquitous in biology, with over 100 distinct modifications. While the vast majority were identified and characterized on abundant noncoding RNA such as tRNA and rRNA, the advent of sensitive sequencing-based approaches has led to the discovery of extensive and regulated modification of eukaryotic messenger RNAs as well. The two most abundant mRNA modifications-pseudouridine (Ψ) and N(6)-methyladenosine (m(6)A)-affect diverse cellular processes including mRNA splicing, localization, translation, and decay and modulate RNA structure...
May 2017: RNA
https://www.readbyqxmd.com/read/28121234/human-m-6-a-writers-two-subunits-2-roles
#19
Xiang Wang, Jinbo Huang, Tingting Zou, Ping Yin
Cellular RNAs with diverse chemical modifications have been observed, and N(6)-methyladenosine (m(6)A) is one of the most abundant internal modifications found on mRNA and non-coding RNAs, playing a vital role in diverse biologic processes. In humans, m(6)A modification is catalyzed by the METTL3-METTL14 methyltransferase complex, which is regulated by WTAP and another factor. Three groups have recently and independently reported the structure of this complex with or without cofactors. Here, we focus on the detailed mechanism of the m(6)A methyltransferase complex and the properties of each subunit...
March 4, 2017: RNA Biology
https://www.readbyqxmd.com/read/28106072/ythdf3-facilitates-translation-and-decay-of-n-6-methyladenosine-modified-rna
#20
Hailing Shi, Xiao Wang, Zhike Lu, Boxuan S Zhao, Honghui Ma, Phillip J Hsu, Chang Liu, Chuan He
N(6)-methyladenosine (m(6)A) is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs), and plays important roles in cell differentiation and tissue development. It regulates multiple steps throughout the RNA life cycle including RNA processing, translation, and decay, via the recognition by selective binding proteins. In the cytoplasm, m(6)A binding protein YTHDF1 facilitates translation of m(6)A-modified mRNAs, and YTHDF2 accelerates the decay of m(6)A-modified transcripts. The biological function of YTHDF3, another cytoplasmic m(6)A binder of the YTH (YT521-B homology) domain family, remains unknown...
March 2017: Cell Research
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