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N-6-methyladenosine RNA

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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
#1
Ahmed S Warda, Jens Kretschmer, Philipp Hackert, Christof Lenz, Henning Urlaub, Claudia Höbartner, Katherine E Sloan, Markus T Bohnsack
N(6)-methyladenosine (m(6)A) is a highly dynamic RNA modification that has recently emerged as a key regulator of gene expression. While many m(6)A modifications are installed by the METTL3-METTL14 complex, others appear to be introduced independently, implying that additional human m(6)A methyltransferases remain to be identified. Using crosslinking and analysis of cDNA (CRAC), we reveal that the putative human m(6)A "writer" protein METTL16 binds to the U6 snRNA and other ncRNAs as well as numerous lncRNAs and pre-mRNAs...
October 19, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29043484/the-role-of-yeast-m-6-a-methyltransferase-in-peroxisomal-fatty-acid-oxidation
#2
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
#3
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
#4
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
#5
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
#6
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 (s(4)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...
September 25, 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
#7
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
https://www.readbyqxmd.com/read/28923956/arabidopsis-m-6-a-demethylase-activity-modulates-viral-infection-of-a-plant-virus-and-the-m-6-a-abundance-in-its-genomic-rnas
#8
Mireya Martínez-Pérez, Frederic Aparicio, Maria Pilar López-Gresa, Jose María Bellés, Jesus A Sánchez-Navarro, Vicente Pallás
N(6)-methyladenosine (m(6)A) is an internal, reversible nucleotide modification that constitutes an important regulatory mechanism in RNA biology. Unlike mammals and yeast, no component of the m(6)A cellular machinery has been described in plants at present. m(6)A has been identified in the genomic RNAs of diverse mammalian viruses and, additionally, viral infection was found to be modulated by the abundance of m(6)A in viral RNAs. Here we show that the Arabidopsis thaliana protein atALKBH9B (At2g17970) is a demethylase that removes m(6)A from single-stranded RNA molecules in vitro...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28914256/mettl3-mettl14-mediated-mrna-n-6-methyladenosine-modulates-murine-spermatogenesis
#9
Zhen Lin, Phillip J Hsu, Xudong Xing, Jianhuo Fang, Zhike Lu, Qin Zou, Ke-Jia Zhang, Xiao Zhang, Yuchuan Zhou, Teng Zhang, Youcheng Zhang, Wanlu Song, Guifang Jia, Xuerui Yang, Chuan He, Ming-Han Tong
Spermatogenesis is a differentiation process during which diploid spermatogonial stem cells (SSCs) produce haploid spermatozoa. This highly specialized process is precisely controlled at the transcriptional, posttranscriptional, and translational levels. Here we report that N(6)-methyladenosine (m(6)A), an epitranscriptomic mark regulating gene expression, plays essential roles during spermatogenesis. We present comprehensive m(6)A mRNA methylomes of mouse spermatogenic cells from five developmental stages: undifferentiated spermatogonia, type A1 spermatogonia, preleptotene spermatocytes, pachytene/diplotene spermatocytes, and round spermatids...
October 2017: Cell Research
https://www.readbyqxmd.com/read/28912888/sulforaphane-induced-cell-cycle-arrest-and-senescence-are-accompanied-by-dna-hypomethylation-and-changes-in-microrna-profile-in-breast-cancer-cells
#10
Anna Lewinska, Jagoda Adamczyk-Grochala, Anna Deregowska, Maciej Wnuk
Cancer cells are characterized by genetic and epigenetic alterations and phytochemicals, epigenetic modulators, are considered as promising candidates for epigenetic therapy of cancer. In the present study, we have investigated cancer cell fates upon stimulation of breast cancer cells (MCF-7, MDA-MB-231, SK-BR-3) with low doses of sulforaphane (SFN), an isothiocyanate. SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence, whereas at the concentration of 20 µM, apoptosis was induced...
2017: Theranostics
https://www.readbyqxmd.com/read/28901284/correction-n-6-methyladenosine-of-hiv-1-rna-regulates-viral-infection-and-hiv-1-gag-protein-expression
#11
Nagaraja Tirumuru, Boxuan Simen Zhao, Wuxun Lu, Zhike Lu, Chuan He, Li Wu
No abstract text is available yet for this article.
September 13, 2017: ELife
https://www.readbyqxmd.com/read/28878038/the-requirement-of-mettl3-promoted-myod-mrna-maintenance-in-proliferative-myoblasts-for-skeletal-muscle-differentiation
#12
Kensuke Kudou, Tetsuro Komatsu, Jumpei Nogami, Kazumitsu Maehara, Akihito Harada, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, Yasuyuki Ohkawa
Myogenic progenitor/stem cells retain their skeletal muscle differentiation potential by maintaining myogenic transcription factors such as MyoD. However, the mechanism of how MyoD expression is maintained in proliferative progenitor cells has not been elucidated. Here, we found that MyoD expression was reduced at the mRNA level by cell cycle arrest in S and G2 phases, which in turn led to the absence of skeletal muscle differentiation. The reduction of MyoD mRNA was correlated with the reduced expression of factors regulating RNA metabolism, including methyltransferase like 3 (Mettl3), which induces N(6)-methyladenosine (m(6)A) modifications of RNA...
September 2017: Open Biology
https://www.readbyqxmd.com/read/28869969/m-6-a-modulates-haematopoietic-stem-and-progenitor-cell-specification
#13
Chunxia Zhang, Yusheng Chen, Baofa Sun, Lu Wang, Ying Yang, Dongyuan Ma, Junhua Lv, Jian Heng, Yanyan Ding, Yuanyuan Xue, Xinyan Lu, Wen Xiao, Yun-Gui Yang, Feng Liu
N(6)-methyladenosine (m(6)A) has been identified as the most abundant modification on eukaryote messenger RNA (mRNA). Although the rapid development of high-throughput sequencing technologies has enabled insight into the biological functions of m(6)A modification, the function of m(6)A during vertebrate embryogenesis remains poorly understood. Here we show that m(6)A determines cell fate during the endothelial-to-haematopoietic transition (EHT) to specify the earliest haematopoietic stem/progenitor cells (HSPCs) during zebrafish embryogenesis...
September 14, 2017: Nature
https://www.readbyqxmd.com/read/28869609/n-6-methyladenosine-m-6-a-recruits-and-repels-proteins-to-regulate-mrna-homeostasis
#14
Raghu R Edupuganti, Simon Geiger, Rik G H Lindeboom, Hailing Shi, Phillip J Hsu, Zhike Lu, Shuang-Yin Wang, Marijke P A Baltissen, Pascal W T C Jansen, Martin Rossa, Markus Müller, Hendrik G Stunnenberg, Chuan He, Thomas Carell, Michiel Vermeulen
RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N(6)-methyladenosine (m(6)A), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to m(6)A to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of m(6)A interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by m(6)A and positively regulates mRNA stability in an m(6)A-regulated manner...
October 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28867294/the-rna-m-6-a-reader-ythdf2-is-essential-for-the-post-transcriptional-regulation-of-the-maternal-transcriptome-and-oocyte-competence
#15
Ivayla Ivanova, Christian Much, Monica Di Giacomo, Chiara Azzi, Marcos Morgan, Pedro N Moreira, Jack Monahan, Claudia Carrieri, Anton J Enright, Dónal O'Carroll
YTHDF2 binds and destabilizes N(6)-methyladenosine (m(6)A)-modified mRNA. The extent to which this branch of m(6)A RNA-regulatory pathway functions in vivo and contributes to mammalian development remains unknown. Here we find that YTHDF2 deficiency is partially permissive in mice and results in female-specific infertility. Using conditional mutagenesis, we demonstrate that YTHDF2 is autonomously required within the germline to produce MII oocytes that are competent to sustain early zygotic development. Oocyte maturation is associated with a wave of maternal RNA degradation, and the resulting relative changes to the MII transcriptome are integral to oocyte quality...
September 21, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28867248/roles-of-rna-methylation-by-means-of-n-6-methyladenosine-m-6-a-in-human-cancers
#16
Siwei Wang, Chunxiao Sun, Jianhua Li, Erbao Zhang, Zhifei Ma, Weizhang Xu, Hong Li, Mantang Qiu, Youtao Xu, Wenjia Xia, Lin Xu, Rong Yin
Reversible methylation by means of N6-methyladenosine (m(6)A) is the most prevalent internal modification in mammalian mRNA. This RNA chemical mark is created by proteins that are m(6)A "writers" and can be reversed by proteins that are m(6)A "erasers" (i.e., demethylases). Some other proteins serving as "readers" can recognize m(6)A-containing mRNA and regulate downstream molecular mechanisms accordingly. Although m(6)A bases in RNA perform critical functions in important biological processes, their roles in cancer biology and cancer stem cells remain largely unknown...
September 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28854373/genome-wide-maps-of-m6a-circrnas-identify-widespread-and-cell-type-specific-methylation-patterns-that-are-distinct-from-mrnas
#17
Chan Zhou, Benoit Molinie, Kaveh Daneshvar, Joshua V Pondick, Jinkai Wang, Nicholas Van Wittenberghe, Yi Xing, Cosmas C Giallourakis, Alan C Mullen
N(6)-methyladenosine (m(6)A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m(6)A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that, together with depletion of ribosomal RNA and m(6)A immunoprecipitation, defined thousands of m(6)A circRNAs with cell-type-specific expression. The presence of m(6)A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m(6)A sites in mRNAs, and by reduced m(6)A levels upon depletion of METTL3, the m(6)A writer...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28846086/the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#18
Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao
DEAD-box (DDX) helicases are vital for the recognition of RNA and metabolism and are critical for the initiation of antiviral innate immunity. Modification of RNA is involved in many biological processes; however, its role in antiviral innate immunity has remained unclear. Here we found that nuclear DDX member DDX46 inhibited the production of type I interferons after viral infection. DDX46 bound Mavs, Traf3 and Traf6 transcripts (which encode signaling molecules involved in antiviral responses) via their conserved CCGGUU element...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28792938/m-6-a-mrna-methylation-controls-t-cell-homeostasis-by-targeting-the-il-7-stat5-socs-pathways
#19
Hua-Bing Li, Jiyu Tong, Shu Zhu, Pedro J Batista, Erin E Duffy, Jun Zhao, Will Bailis, Guangchao Cao, Lina Kroehling, Yuanyuan Chen, Geng Wang, James P Broughton, Y Grace Chen, Yuval Kluger, Matthew D Simon, Howard Y Chang, Zhinan Yin, Richard A Flavell
N(6)-methyladenosine (m(6)A) is the most common and abundant messenger RNA modification, modulated by 'writers', 'erasers' and 'readers' of this mark. In vitro data have shown that m(6)A influences all fundamental aspects of mRNA metabolism, mainly mRNA stability, to determine stem cell fates. However, its in vivo physiological function in mammals and adult mammalian cells is still unknown. Here we show that the deletion of m(6)A 'writer' protein METTL3 in mouse T cells disrupts T cell homeostasis and differentiation...
August 17, 2017: Nature
https://www.readbyqxmd.com/read/28705773/recent-progress-in-circular-rnas-in-human-cancers
#20
Guanqun Huang, Shuaihu Li, Nuo Yang, Yongdong Zou, Duo Zheng, Tian Xiao
Circular RNAs (circRNAs) are a large class of endogenous RNAs, formed by exon skipping or back-splicing events as covalently closed loops, which are expressed abundantly in mammalian cells. Although their biological functions remain largely unknown, recent studies show that circRNAs have three main functions in mammalian cells. First, circRNAs can regulate transcription and RNA splicing. Second, circRNAs function as microRNA (miRNA) sponges. Third, they can be translated into protein driven by N(6)-methyladenosine modification...
September 28, 2017: Cancer Letters
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