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N-6-methyladenosine RNA

Annita Louloupi, Evgenia Ntini, Thomas Conrad, Ulf Andersson Vang Ørom
Splicing efficiency varies among transcripts, and tight control of splicing kinetics is crucial for coordinated gene expression. N-6-methyladenosine (m6A) is the most abundant RNA modification and is involved in regulation of RNA biogenesis and function. The impact of m6A on regulation of RNA splicing kinetics is unknown. Here, we provide a time-resolved high-resolution assessment of m6A on nascent RNA transcripts and unveil its importance for the control of RNA splicing kinetics. We find that early co-transcriptional m6A deposition near splice junctions promotes fast splicing, while m6A modifications in introns are associated with long, slowly processed introns and alternative splicing events...
June 19, 2018: Cell Reports
Yang Wang, Yue Li, Minghui Yue, Jun Wang, Sandeep Kumar, Robert J Wechsler-Reya, Zhaolei Zhang, Yuya Ogawa, Manolis Kellis, Gregg Duester, Jing Crystal Zhao
In the version of this article initially published online, there were errors in URLs for, appearing in Methods sections "m6A dot-blot" and "Western blot analysis." The first two URLs should be and the third should be In addition, some Methods URLs for, and were printed correctly but not properly linked...
June 7, 2018: Nature Neuroscience
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
In the version of this Article originally published, the authors incorrectly listed an accession code as GES90642. The correct code is GSE90642 . This has now been amended in all online versions of the Article.
June 7, 2018: Nature Cell Biology
Jidong Zhang, Pengmian Feng, Hao Lin, Wei Chen
N6 -methyladenosine (m6 A) plays important roles in a branch of biological and physiological processes. Accurate identification of m6 A sites is especially helpful for understanding their biological functions. Since the wet-lab techniques are still expensive and time-consuming, it's urgent to develop computational methods to identify m6 A sites from primary RNA sequences. Although there are some computational methods for identifying m6 A sites, no methods whatsoever are available for detecting m6 A sites in microbial genomes...
2018: Frontiers in Microbiology
Masatoshi Kobayashi, Mitsuru Ohsugi, Takayoshi Sasako, Motoharu Awazawa, Toshihiro Umehara, Aya Iwane, Naoki Kobayashi, Yukiko Okazaki, Naoto Kubota, Ryo Suzuki, Hironori Waki, Keiko Horiuchi, Takao Hamakubo, Tatsuhiko Kodama, Seiichiro Aoe, Kazuyuki Tobe, Takashi Kadowaki, Kohjiro Ueki
Adipocyte differentiation is regulated by various mechanisms, of which the mitotic clonal expansion (MCE) is a key step. Although this process is known to be regulated by the cell cycle modulators, the precise mechanism remains unclear. N 6 -methyladenosine (m6 A) post-transcriptional RNA modification, whose methylation and demethylation is performed by respective enzymal molecules, has recently been suggested to be involved in the regulation of adipogenesis. Here, we show that an RNA N 6 -adenosine methyltransferase complex consisting of Wilms' tumor 1-associating protein (WTAP), methyltransferase like (METTL) 3 and METTL14 positively control adipogenesis, by promoting cell cycle transition in MCE during adipogenesis...
June 4, 2018: Molecular and Cellular Biology
Tongxing Song, Jinxin Lu, Zhao Deng, Tao Xu, Yue Yang, Hongkui Wei, Shengqing Li, Siwen Jiang, Jian Peng
BACKGROUND: The growing prevalence of overweight or obese pregnancies shows an increasing risk for aberrant fetal growth and postnatal complications. Maternal obesity is associated with low birth weight (LBW) of piglets. However, the development of LBW from maternal obesity is not well understood. OBJECTIVE: This study attempts to investigate the novel RNA modification N6-methyladenosine (m6 A) in the placenta tissues by using sows with high backfat thickness as a model for obese pregnancy...
May 24, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Weiliang Liu, Jingli Yan, Zhenhao Zhang, Hongru Pian, Chenghui Liu, Zhengping Li
N 6 -Methyladenosine (m6 A) is the most frequent post-transcriptional modification in RNA, and it plays a critical role in biological processes. The functions of m6 A remain largely unexplored due to a lack of highly sensitive methods to quantitatively determine the m6 A modification fraction at a precise location. Here, we first reveal that T3 DNA ligase has significant selectivity towards the m6 A modification. On the basis of the new finding, we establish an ultrasensitive quantitation assay for accurately determining m6 A at one-nucleotide resolution in RNA...
April 7, 2018: Chemical Science
Sicong Zhang
N6 -methyladenosine (m6 A), the most prevalent internal methylation in messenger RNA (mRNA) that is deposited by m6 A methyltransferases, removed by m6 A demethylases and recognized by different RNA-binding proteins, distinguishes the transcripts through multilayer interactions with mRNA processing, export, degradation and translation machineries. m6 A plays an important role in regulation of gene expression for fundamental cellular processes and diverse physiological functions. Aberrant m6 A decorations lead to cancer but also have the potential to yield new therapies...
May 3, 2018: Pharmacology & Therapeutics
Shanhui Liao, Hongbin Sun, Chao Xu
Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N6 -methyladenosine (m6 A) is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs (lncRNAs). In mammalian cells, m6 A can be incorporated by a methyltransferase complex and removed by demethylases, which ensures that the m6 A modification is reversible and dynamic...
April 2018: Genomics, Proteomics & Bioinformatics
Jinbo Huang, Ping Yin
More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6 -methyladenosine (m6 A), have been detected in mRNA, opening the window into the realm of epitranscriptomics. The m6 A modification is the most abundant modification in mRNA and non-coding RNA (ncRNA). At the molecular level, m6 A affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA (miRNA) maturation, playing essential roles in a range of cellular processes...
April 2018: Genomics, Proteomics & Bioinformatics
Brandon Tan, Shou-Jiang Gao
N6 -methyladenosine (m6 A) was discovered 4 decades ago. However, the functions of m6 A and the cellular machinery that regulates its changes have just been revealed in the last few years. m6 A is an abundant internal mRNA modification on cellular RNA and is implicated in diverse cellular functions. Recent works have demonstrated the presence of m6 A in the genomes of RNA viruses and transcripts of a DNA virus with either a proviral or antiviral role. Here, we first summarize what is known about the m6 A "writers," "erasers," "readers," and "antireaders" as well as the role of m6 A in mRNA metabolism...
April 26, 2018: Reviews in Medical Virology
Xiaolan Deng, Rui Su, Hengyou Weng, Huilin Huang, Zejuan Li, Jianjun Chen
N6 -methyladenosine (m6 A), the most abundant internal modification in eukaryotic messenger RNAs (mRNAs), has been shown to play critical roles in various normal bioprocesses such as tissue development, stem cell self-renewal and differentiation, heat shock or DNA damage response, and maternal-to-zygotic transition. The m6 A modification is deposited by the m6 A methyltransferase complex (MTC; i.e., writer) composed of METTL3, METTL14 and WTAP, and probably also VIRMA and RBM15, and can be removed by m6 A demethylases (i...
May 2018: Cell Research
Shiyan Gu, Donglei Sun, Huangmei Dai, Zunzhen Zhang
N6 -methyladenosine (m6 A) modification is implicated to play an important role in cellular biological processes, but its regulatory mechanisms in arsenite-induced carcinogenesis are largely unknown. Here, human bronchial epithelial (HBE) cells were chronically treated with 2.5 μM arsenite sodium (NaAsO2 ) for about 13 weeks and these cells were identified with malignant phenotype which was demonstrated by increased levels of cellular proliferation, percentages of plate colony formation and soft agar clone formation, and high potential of resistance to apoptotic induction...
August 2018: Toxicology Letters
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
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
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...
April 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
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
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...
June 15, 2018: Biosensors & Bioelectronics
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
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
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