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N-6-methyladenosine RNA

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https://www.readbyqxmd.com/read/28106072/ythdf3-facilitates-translation-and-decay-of-n-6-methyladenosine-modified-rna
#1
Hailing Shi, Xiao Wang, Zhike Lu, Boxuan S Zhao, Honghui Ma, Phillip J Hsu, 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...
January 20, 2017: Cell Research
https://www.readbyqxmd.com/read/28079126/detecting-n-6-methyladenosine-sites-from-rna-transcriptomes-using-ensemble-support-vector-machines
#2
Wei Chen, Pengwei Xing, Quan Zou
As one of the most abundant RNA post-transcriptional modifications, N(6)-methyladenosine (m(6)A) involves in a broad spectrum of biological and physiological processes ranging from mRNA splicing and stability to cell differentiation and reprogramming. However, experimental identification of m(6)A sites is expensive and laborious. Therefore, it is urgent to develop computational methods for reliable prediction of m(6)A sites from primary RNA sequences. In the current study, a new method called RAM-ESVM was developed for detecting m(6)A sites from Saccharomyces cerevisiae transcriptome, which employed ensemble support vector machine classifiers and novel sequence features...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28060253/a-method-for-measuring-rna-n-6-methyladenosine-modifications-in-cells-and-tissues
#3
Chao-Yung Wang, Mei-Hsiu Lin, Hui-Ting Su
N(6)-Methyladenosine (m(6)A) modifications of RNA are diverse and ubiquitous amongst eukaryotes. They occur in mRNA, rRNA, tRNA, and microRNA. Recent studies have revealed that these reversible RNA modifications affect RNA splicing, translation, degradation, and localization. Multiple physiological processes, like circadian rhythms, stem cell pluripotency, fibrosis, triglyceride metabolism, and obesity are also controlled by m(6)A modifications. Immunoprecipitation/sequencing, mass spectrometry, and modified northern blotting are some of the methods commonly employed to measure m(6)A modifications...
December 5, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28017614/fto-plays-an-oncogenic-role-in-acute-myeloid-leukemia-as-a-n-6-methyladenosine-rna-demethylase
#4
Zejuan Li, Hengyou Weng, Rui Su, Xiaocheng Weng, Zhixiang Zuo, Chenying Li, Huilin Huang, Sigrid Nachtergaele, Lei Dong, Chao Hu, Xi Qin, Lichun Tang, Yungui Wang, Gia-Ming Hong, Hao Huang, Xiao Wang, Ping Chen, Sandeep Gurbuxani, Stephen Arnovitz, Yuanyuan Li, Shenglai Li, Jennifer Strong, Mary Beth Neilly, Richard A Larson, Xi Jiang, Pumin Zhang, Jie Jin, Chuan He, Jianjun Chen
N(6)-Methyladenosine (m(6)A) represents the most prevalent internal modification in mammalian mRNAs. Despite its functional importance in various fundamental bioprocesses, the studies of m(6)A in cancer have been limited. Here we show that FTO, as an m(6)A demethylase, plays a critical oncogenic role in acute myeloid leukemia (AML). FTO is highly expressed in AMLs with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations. FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and RARA by reducing m(6)A levels in these mRNA transcripts...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/27919081/m-6-a-potentiates-sxl-alternative-pre-mrna-splicing-for-robust-drosophila-sex-determination
#5
Irmgard U Haussmann, Zsuzsanna Bodi, Eugenio Sanchez-Moran, Nigel P Mongan, Nathan Archer, Rupert G Fray, Matthias Soller
N(6)-methyladenosine (m(6)A) is the most common internal modification of eukaryotic messenger RNA (mRNA) and is decoded by YTH domain proteins. The mammalian mRNA m(6)A methylosome is a complex of nuclear proteins that includes METTL3 (methyltransferase-like 3), METTL14, WTAP (Wilms tumour 1-associated protein) and KIAA1429. Drosophila has corresponding homologues named Ime4 and KAR4 (Inducer of meiosis 4 and Karyogamy protein 4), and Female-lethal (2)d (Fl(2)d) and Virilizer (Vir). In Drosophila, fl(2)d and vir are required for sex-dependent regulation of alternative splicing of the sex determination factor Sex lethal (Sxl)...
December 8, 2016: Nature
https://www.readbyqxmd.com/read/27919077/m-6-a-modulates-neuronal-functions-and-sex-determination-in-drosophila
#6
Tina Lence, Junaid Akhtar, Marc Bayer, Katharina Schmid, Laura Spindler, Cheuk Hei Ho, Nastasja Kreim, Miguel A Andrade-Navarro, Burkhard Poeck, Mark Helm, Jean-Yves Roignant
N(6)-methyladenosine RNA (m(6)A) is a prevalent messenger RNA modification in vertebrates. Although its functions in the regulation of post-transcriptional gene expression are beginning to be unveiled, the precise roles of m(6)A during development of complex organisms remain unclear. Here we carry out a comprehensive molecular and physiological characterization of the individual components of the methyltransferase complex, as well as of the YTH domain-containing nuclear reader protein in Drosophila melanogaster...
December 8, 2016: Nature
https://www.readbyqxmd.com/read/27913822/more-than-just-scanning-the-importance-of-cap-independent-mrna-translation-initiation-for-cellular-stress-response-and-cancer
#7
REVIEW
Rafaela Lacerda, Juliane Menezes, Luísa Romão
The scanning model for eukaryotic mRNA translation initiation states that the small ribosomal subunit, along with initiation factors, binds at the cap structure at the 5' end of the mRNA and scans the 5' untranslated region (5'UTR) until an initiation codon is found. However, under conditions that impair canonical cap-dependent translation, the synthesis of some proteins is kept by alternative mechanisms that are required for cell survival and stress recovery. Alternative modes of translation initiation include cap- and/or scanning-independent mechanisms of ribosomal recruitment...
December 2, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27856248/mir-33a-suppresses-proliferation-of-nsclc-cells-via-targeting-mettl3-mrna
#8
Minjun Du, Yanjiao Zhang, Yousheng Mao, Juwei Mou, Jun Zhao, Qi Xue, Dali Wang, Jinfeng Huang, Shugeng Gao, Yushun Gao
Methyltransferase like 3 (METTL3) was incipiently known as a methyltransferase which was responsible for N(6)-methyladenosine (m(6)A) methylation. METTL3 can promote the expression of several crucial oncoproteins and its high expression enhanced proliferation, survival, and invasion of human lung cancer cells. However, how METTL3 was regulated is seldom understood in non-small-cell lung carcinoma (NSCLC). In the present study, miR-33a was suspicious to target to the 3'-untranslated region (3'UTR) of METTL3 mRNA via in silico prediction...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27808276/post-transcriptional-gene-regulation-by-mrna-modifications
#9
Boxuan Simen Zhao, Ian A Roundtree, Chuan He
The recent discovery of reversible mRNA methylation has opened a new realm of post-transcriptional gene regulation in eukaryotes. The identification and functional characterization of proteins that specifically recognize RNA N(6)-methyladenosine (m(6)A) unveiled it as a modification that cells utilize to accelerate mRNA metabolism and translation. N(6)-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses...
January 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/27803056/post-transcriptional-modifications-in-development-and-stem-cells
#10
REVIEW
Michaela Frye, Sandra Blanco
Cells adapt to their environment by linking external stimuli to an intricate network of transcriptional, post-transcriptional and translational processes. Among these, mechanisms that couple environmental cues to the regulation of protein translation are not well understood. Chemical modifications of RNA allow rapid cellular responses to external stimuli by modulating a wide range of fundamental biochemical properties and processes, including the stability, splicing and translation of messenger RNA. In this Review, we focus on the occurrence of N(6)-methyladenosine (m(6)A), 5-methylcytosine (m(5)C) and pseudouridine (Ψ) in RNA, and describe how these RNA modifications are implicated in regulating pluripotency, stem cell self-renewal and fate specification...
November 1, 2016: Development
https://www.readbyqxmd.com/read/27651356/rnas-containing-modified-nucleotides-fail-to-trigger-rig-i-conformational-changes-for-innate-immune-signaling
#11
Ann Fiegen Durbin, Chen Wang, Joseph Marcotrigiano, Lee Gehrke
UNLABELLED: Invading pathogen nucleic acids are recognized and bound by cytoplasmic (retinoic acid-inducible gene I [RIG-I]-like) and membrane-bound (Toll-like) pattern recognition receptors to activate innate immune signaling. Modified nucleotides, when present in RNA molecules, diminish the magnitude of these signaling responses. However, mechanisms explaining the blunted signaling have not been elucidated. In this study, we used several independent biological assays, including inhibition of virus replication, RIG-I:RNA binding assays, and limited trypsin digestion of RIG-I:RNA complexes, to begin to understand how RNAs containing modified nucleotides avoid or suppress innate immune signaling...
September 20, 2016: MBio
https://www.readbyqxmd.com/read/27647213/emerging-themes-in-regulation-of-global-mrna-turnover-in-cis
#12
REVIEW
Chyi-Ying A Chen, Ann-Bin Shyu
mRNA is the molecule that conveys genetic information from DNA to the translation apparatus. mRNAs in all organisms display a wide range of stability, and mechanisms have evolved to selectively and differentially regulate individual mRNA stability in response to intracellular and extracellular cues. In recent years, three seemingly distinct aspects of RNA biology-mRNA N(6)-methyladenosine (m6A) modification, alternative 3' end processing and polyadenylation (APA), and mRNA codon usage-have been linked to mRNA turnover, and all three aspects function to regulate global mRNA stability in cis...
January 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27602518/m-6-a-rna-methylation-promotes-xist-mediated-transcriptional-repression
#13
Deepak P Patil, Chun-Kan Chen, Brian F Pickering, Amy Chow, Constanza Jackson, Mitchell Guttman, Samie R Jaffrey
The long non-coding RNA X-inactive specific transcript (XIST) mediates the transcriptional silencing of genes on the X chromosome. Here we show that, in human cells, XIST is highly methylated with at least 78 N(6)-methyladenosine (m(6)A) residues-a reversible base modification of unknown function in long non-coding RNAs. We show that m(6)A formation in XIST, as well as in cellular mRNAs, is mediated by RNA-binding motif protein 15 (RBM15) and its paralogue RBM15B, which bind the m(6)A-methylation complex and recruit it to specific sites in RNA...
September 15, 2016: Nature
https://www.readbyqxmd.com/read/27572442/dynamics-of-the-human-and-viral-m-6-a-rna-methylomes-during-hiv-1-infection-of-t-cells
#14
Gianluigi Lichinchi, Shang Gao, Yogesh Saletore, Gwendolyn Michelle Gonzalez, Vikas Bansal, Yinsheng Wang, Christopher E Mason, Tariq M Rana
N(6)-methyladenosine (m(6)A) is the most prevalent internal modification of eukaryotic mRNA. Very little is known of the function of m(6)A in the immune system or its role in host-pathogen interactions. Here, we investigate the topology, dynamics and bidirectional influences of the viral-host RNA methylomes during HIV-1 infection of human CD4 T cells. We show that viral infection triggers a massive increase in m(6)A in both host and viral mRNAs. In HIV-1 mRNA, we identified 14 methylation peaks in coding and noncoding regions, splicing junctions and splicing regulatory sequences...
2016: Nature Microbiology
https://www.readbyqxmd.com/read/27556597/a-hierarchical-model-for-clustering-m-6-a-methylation-peaks-in-merip-seq-data
#15
Xiaodong Cui, Jia Meng, Shaowu Zhang, Manjeet K Rao, Yidong Chen, Yufei Huang
BACKGROUND: The recent advent of the state-of-art high throughput sequencing technology, known as Methylated RNA Immunoprecipitation combined with RNA sequencing (MeRIP-seq) revolutionizes the area of mRNA epigenetics and enables the biologists and biomedical researchers to have a global view of N (6)-Methyladenosine (m(6)A) on transcriptome. Yet there is a significant need for new computation tools for processing and analysing MeRIP-Seq data to gain a further insight into the function and m(6)A mRNA methylation...
2016: BMC Genomics
https://www.readbyqxmd.com/read/27396363/n-6-methyladenosine-rna-modification-regulates-shoot-stem-cell-fate-in-arabidopsis
#16
Lisha Shen, Zhe Liang, Xiaofeng Gu, Ying Chen, Zhi Wei Norman Teo, Xingliang Hou, Weiling Maggie Cai, Peter C Dedon, Lu Liu, Hao Yu
N(6)-Methyladenosine (m(6)A) represents the most prevalent internal modification on mRNA and requires a multicomponent m(6)A methyltransferase complex in mammals. How their plant counterparts determine the global m(6)A modification landscape and its molecular link to plant development remain unknown. Here we show that FKBP12 INTERACTING PROTEIN 37 KD (FIP37) is a core component of the m(6)A methyltransferase complex, which underlies control of shoot stem cell fate in Arabidopsis. The mutants lacking FIP37 exhibit massive overproliferation of shoot meristems and a transcriptome-wide loss of m(6)A RNA modifications...
July 25, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27376769/m-6-a-laic-seq-reveals-the-census-and-complexity-of-the-m-6-a-epitranscriptome
#17
Benoit Molinie, Jinkai Wang, Kok Seong Lim, Roman Hillebrand, Zhi-Xiang Lu, Nicholas Van Wittenberghe, Benjamin D Howard, Kaveh Daneshvar, Alan C Mullen, Peter Dedon, Yi Xing, Cosmas C Giallourakis
N(6)-Methyladenosine (m(6)A) is a widespread, reversible chemical modification of RNA molecules, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m(6)A modified ('m(6)A levels') or the relationship of m(6)A modification(s) to alternative RNA isoforms. To deconvolute the m(6)A epitranscriptome, we developed m(6)A-level and isoform-characterization sequencing (m(6)A-LAIC-seq). We found that cells exhibit a broad range of nonstoichiometric m(6)A levels with cell-type specificity...
August 2016: Nature Methods
https://www.readbyqxmd.com/read/27371828/n-6-methyladenosine-of-hiv-1-rna-regulates-viral-infection-and-hiv-1-gag-protein-expression
#18
Nagaraja Tirumuru, Boxuan Simen Zhao, Wuxun Lu, Zhike Lu, Chuan He, Li Wu
The internal N(6)-methyladenosine (m(6)A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m(6)A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1-3) bind to m(6)A-modified cellular RNAs and affect RNA metabolism and processing. Here, we show that YTHDF1-3 proteins recognize m(6)A-modified HIV-1 RNA and inhibit HIV-1 infection in cell lines and primary CD4(+) T-cells...
2016: ELife
https://www.readbyqxmd.com/read/27351916/mrna-modifications-dynamic-regulators-of-gene-expression
#19
Thomas Philipp Hoernes, Alexander Hüttenhofer, Matthias David Erlacher
The expression of a gene is a tightly regulated process and is exerted by a myriad of different mechanisms. Recently, RNA modifications located in coding sequences of mRNAs, have been identified as potential regulators of gene expression. N(6)-methyladenosine (m(6)A), 5-methylcytosine (m(5)C), pseudouridine (Ψ) and N(1)-methyladenosine (m(1)A) have been found within open reading frames of mRNAs. The presence of these mRNA modifications has been implicated to modulate the fate of an mRNA, ranging from maturation to its translation and even degradation...
September 2016: RNA Biology
https://www.readbyqxmd.com/read/27345446/translating-the-epitranscriptome
#20
REVIEW
Thomas Philipp Hoernes, Matthias David Erlacher
RNA modifications are indispensable for the translation machinery to provide accurate and efficient protein synthesis. Whereas the importance of transfer RNA (tRNA) and ribosomal RNA (rRNA) modifications has been well described and is unquestioned for decades, the significance of internal messenger RNA (mRNA) modifications has only recently been revealed. Novel experimental methods have enabled the identification of thousands of modified sites within the untranslated and translated regions of mRNAs. Thus far, N(6) -methyladenosine (m(6) A), pseudouridine (Ψ), 5-methylcytosine (m(5) C) and N(1) -methyladenosine (m(1) A) were identified in eukaryal, and to some extent in prokaryal mRNAs...
January 2017: Wiley Interdisciplinary Reviews. RNA
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