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Shu-Jing Liu, Hui-Ling Tang, Qian He, Ping Lu, Tao Fu, Xu-Ling Xu, Tao Su, Mei-Mei Gao, Shumin Duan, Yan Luo, Yue-Sheng Long
Fat mass and obesity-associated (FTO) protein is a ferrous ion (Fe2+)/2-oxoglutarate (2-OG)-dependent demethylase preferentially catalyzing m6A sites in RNA. The FTO gene is highly expressed in the hypothalamus with fluctuation in response to various nutritional conditions, which is believed to be involved in the control of whole body metabolism. However, the underlying mechanism in response to different nutritional cues remains poorly understood. Here we show that ketogenic diet-derived ketone body β-hydroxybutyrate (BHB) transiently increases FTO expression in both mouse hypothalamus and cultured cells...
May 16, 2018: Journal of Molecular Cell Biology
Meng-Dan Lan, Jun Xiong, Xue-Jiao You, Xiao-Cheng Weng, Xiang Zhou, Bi-Feng Yuan, Yu-Qi Feng
RNA contains diverse modifications that exert important influences in a variety of cellular processes. So far more than 150 modifications have been identified in various RNA species, mainly in ribosomal RNA (rRNA), transfer RNA (tRNA), and messenger RNA (mRNA). In contrast to rRNA, tRNA and mRNA, the known modifications in small RNAs have been primarily limited to 2'-O-ribose methylations in plants and inosine in mammals. Methylation of small RNAs in mammals is still unclear. Current methods widely used in the characterization of small RNAs are mainly based on the strategy of nucleic acid hybridization and sequencing, which cannot characterize modifications in small RNAs...
May 14, 2018: Chemistry: a European Journal
Vladimir Potapov, Xiaoqing Fu, Nan Dai, Ivan R Corrêa, Nathan A Tanner, Jennifer L Ong
Ribonucleic acid (RNA) is capable of hosting a variety of chemically diverse modifications, in both naturally-occurring post-transcriptional modifications and artificial chemical modifications used to expand the functionality of RNA. However, few studies have addressed how base modifications affect RNA polymerase and reverse transcriptase activity and fidelity. Here, we describe the fidelity of RNA synthesis and reverse transcription of modified ribonucleotides using an assay based on Pacific Biosciences Single Molecule Real-Time sequencing...
May 10, 2018: Nucleic Acids Research
Jennifer A Lockhart
No abstract text is available yet for this article.
May 8, 2018: Plant Cell
Lian-Huan Wei, Peizhe Song, Ye Wang, Zhike Lu, Qian Tang, Qiong Yu, Yu Xiao, Xiao Zhang, Hong-Chao Duan, Guifang Jia
The epitranscriptomic mark N6-methyladenosine (m6A) can be written, read, and erased via the action of a complex network of proteins. m6A-binding proteins read m6A marks and transduce their downstream regulatory effects by altering RNA metabolic processes. The characterization of m6A readers is an essential prerequisite for understanding the roles of m6A in plants, but the identities of m6A readers have been unclear. Here, we characterized the YTH-domain family protein ECT2 as an Arabidopsis thaliana m6A reader whose m6A-binding function is required for normal trichome morphology...
April 30, 2018: Plant Cell
Charles Hesser, John Karijolich, Dan Dominissini, Chuan He, Britt A Glaunsinger
Methylation at the N6 position of adenosine (m6A) is a highly prevalent and reversible modification within eukaryotic mRNAs that has been linked to many stages of RNA processing and fate. Recent studies suggest that m6A deposition and proteins involved in the m6A pathway play a diverse set of roles in either restricting or modulating the lifecycles of select viruses. Here, we report that m6A levels are significantly increased in cells infected with the oncogenic human DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV)...
April 16, 2018: PLoS Pathogens
Laura Arribas-Hernández, Simon Bressendorff, Mathias Henning Hansen, Christian Poulsen, Susanne Erdmann, Peter Brodersen
Methylation of N6-adenosine (m6A) in mRNA is an important post-transcriptional gene regulatory mechanism in eukaryotes. m6A provides a binding site for effector proteins ("readers") that influence pre-mRNA splicing, mRNA degradation or translational efficiency. YT521-B homology (YTH) domain proteins are important m6A readers with established functions in animals. Plants contain more YTH domain proteins than other eukaryotes, but their biological importance remains unknown. Here, we show that the cytoplasmic Arabidopsis thaliana YTH domain proteins EVOLUTIONARILY CONSERVED C-TERMINAL REGION2/3 (ECT2/3) are required for the correct timing of leaf formation and for normal leaf morphology...
April 11, 2018: Plant Cell
Jérémy Scutenaire, Jean-Marc Deragon, Viviane Jean, Moussa Benhamed, Cécile Raynaud, Jean-Jacques Favory, Rémy Merret, Cécile Bousquet-Antonelli
Methylations at position N6 of internal adenosines (m6As) are the most abundant and widespread mRNA modifications. These modifications play crucial roles in reproduction, growth and development by controlling gene express patterns at the post-transcriptional level. Their function is decoded by readers that share the YTH domain, which forms a hydrophobic pocket that directly accommodates the m6A residues. While the physiological and molecular functions of YTH readers have been extensively studied in animals, little is known about plant readers, even though m6As are crucial for plant survival and development...
April 4, 2018: Plant Cell
Shuai Jiang, Yubin Xie, Zhihao He, Ya Zhang, Yuli Zhao, Li Chen, Yueyuan Zheng, Yanyan Miao, Zhixiang Zuo, Jian Ren
Background: Large-scale genome sequencing projects have identified many genetic variants for diverse diseases. A major goal of these projects is to characterize these genetic variants to provide insight into their function and roles in diseases. N6-methyladenosine (m6A) is one of the most abundant RNA modifications in eukaryotes. Recent studies have revealed that aberrant m6A modifications are involved in many diseases. Findings: In this study, we present a user-friendly web server called "m6ASNP" that is dedicated to the identification of genetic variants targeting m6A modification sites...
April 2, 2018: GigaScience
Ziyu Ma, Yahui Ren, Min Ling, Huayan Wang
In post-transcriptional mRNA modification, m⁶A has been observed in a wide range of eukaryotes. METTL3, as a component of methyltransferase complex for m⁶A modification, regulates mouse naïve pluripotency and influences mRNA stability, especially affecting the expression level of the key pluripotent transcription factors. To reveal the expression pattern of the porcine METTL3 gene, we analyzed METTL3 expression level in different porcine tissues, somatic cells, and induced pluripotent stem cells (piPSCs) by RT-PCR...
March 25, 2018: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Kyung-Won Min, Richard W Zealy, Sylvia Davila, Mikhail Fomin, James C Cummings, Daniel Makowsky, Catherine H Mcdowell, Haley Thigpen, Markus Hafner, Sang-Ho Kwon, Constantin Georgescu, Jonathan D Wren, Je-Hyun Yoon
Gene expression is dynamically regulated in a variety of mammalian physiologies. During mammalian aging, there are changes that occur in protein expression that are highly controlled by the regulatory steps in transcription, post-transcription, and post-translation. Although there are global profiles of human transcripts during the aging processes available, the mechanism(s) by which transcripts are differentially expressed between young and old cohorts remains unclear. Here, we report on N6-methyladenosine (m6A) RNA modification profiles of human peripheral blood mononuclear cells (PBMCs) from young and old cohorts...
March 23, 2018: Aging Cell
Dandan Yang, Jing Qiao, Guiying Wang, Yuanyuan Lan, Guoping Li, Xudong Guo, Jiajie Xi, Dan Ye, Songcheng Zhu, Wen Chen, Wenwen Jia, Ye Leng, Xiaoping Wan, Jiuhong Kang
Previous studies have revealed the critical roles of N6-methyladenosine (m6A) modification of mRNA in embryonic stem cells (ESCs), but the biological function of m6A in large intergenic noncoding RNA (lincRNA) is unknown. Here, we showed that the internal m6A modification of linc1281 mediates a competing endogenous RNA (ceRNA) model to regulate mouse ESC (mESC) differentiation. We demonstrated that loss of linc1281 compromises mESC differentiation and that m6A is highly enriched within linc1281 transcripts...
May 4, 2018: Nucleic Acids Research
Yuzhang Du, Guofang Hou, Hailong Zhang, Jinzhuo Dou, Jianfeng He, Yanming Guo, Lian Li, Ran Chen, Yanli Wang, Rong Deng, Jian Huang, Bin Jiang, Ming Xu, Jinke Cheng, Guo-Qiang Chen, Xian Zhao, Jianxiu Yu
The methyltransferase like 3 (METTL3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for N6-methyladenosine (m6A) modification in diverse RNAs including mRNA, tRNA, rRNA, small nuclear RNA, microRNA precursor and long non-coding RNA. However, the characteristics of METTL3 in activation and post-translational modification (PTM) is seldom understood. Here we find that METTL3 is modified by SUMO1 mainly at lysine residues K177, K211, K212 and K215, which can be reduced by an SUMO1-specific protease SENP1...
February 28, 2018: Nucleic Acids Research
Zhihui Feng, Qimeng Li, Runsha Meng, Baicheng Yi, Qiong Xu
Dental pulp inflammation is a widespread public health problem caused by oral bacterial infections and can progress to pulp necrosis and periapical diseases. N6-methyladenosine (m6A) is a prevalent epitranscriptomic modification in mRNA. Previous studies have demonstrated that m6A methylation plays important roles in cell differentiation, embryonic development and stress responses. However, whether m6A modification affects dental pulp inflammation remains unknown. To address this issue, we investigated the expression of m6A and N6-adenosine methyltransferase (METTL3, METTL14) as well as demethylases (FTO, ALKBH5) and found that the levels of m6A and METTL3 were up-regulated in human dental pulp cells (HDPCs) stimulated by lipopolysaccharide (LPS)...
May 2018: Journal of Cellular and Molecular Medicine
Tingting Hong, Yushu Yuan, Zonggui Chen, Kun Xi, Tianlu Wang, Yalun Xie, Zhiyong He, Haomiao Su, Yu Zhou, Zhi-Jie Tan, Xiaocheng Weng, Xiang Zhou
Innovative detection techniques to achieve precise m6A distribution within mammalian transcriptome can advance our understanding of its biological functions. We specifically introduced the atom-specific replacement of oxygen with progressively larger atoms (sulfur and selenium) at 4-position of deoxythymidine triphosphate to weaken its ability to base pair with m6A, while maintaining A-T* base pair virtually the same as the natural one. 4SedTTP turned out to be an outstanding candidate that endowed m6A with a specific signature of RT truncation, thereby making this "RT-silent" modification detectable with the assistance of m6A demethylase FTO through next-generation sequencing...
May 9, 2018: Journal of the American Chemical Society
Yujiro Nishizawa, Masamitsu Konno, Ayumu Asai, Jun Koseki, Koichi Kawamoto, Norikatsu Miyoshi, Hidekazu Takahashi, Naohiro Nishida, Naotsugu Haraguchi, Daisuke Sakai, Toshihiro Kudo, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Recent studies that have emerged on the diversity of RNA modification in tumors suggest their eligibility as bona fide targets in diagnosis and drug discovery. N6-methyladenosine (m6 A) was first reported and is most common in epitranscriptome modification of various RNAs. The YT521-B homology (YTH) domain family are representative m6A-binding proteins, but how the YTH domain family is involved in cancer remains to be clearly understood. Given that clinical sequence data in colorectal cancer indicate that overexpression of YTHDF1 is outstanding among other family members, we studied the role of Ythdf1 and the transcriptional control of YTHDF1...
January 26, 2018: Oncotarget
Mohea Couturier, Ann-Christin Lindås
DNA methylation is the most common epigenetic modification observed in the genomic DNA (gDNA) of prokaryotes and eukaryotes. Methylated nucleobases, N6 -methyl-adenine (m6A), N4 -methyl-cytosine (m4C), and 5-methyl-cytosine (m5C), detected on gDNA represent the discrimination mark between self and non-self DNA when they are part of restriction-modification systems in prokaryotes (Bacteria and Archaea). In addition, m5C in Eukaryotes and m6A in Bacteria play an important role in the regulation of key cellular processes...
2018: Frontiers in Microbiology
Katja Hartstock, Benedikt S Nilges, Anna Ovcharenko, Nicolas V Cornelissen, Nikolai Püllen, Ann-Marie Lawrence-Dörner, Sebastian A Leidel, Andrea Rentmeister
m6 A is the most abundant internal modification in eukaryotic mRNA. It is introduced by METTL3-METTL14 and tunes mRNA metabolism, impacting cell differentiation and development. Precise transcriptome-wide assignment of m6 A sites is of utmost importance. However, m6 A does not interfere with Watson-Crick base pairing, making polymerase-based detection challenging. We developed a chemical biology approach for the precise mapping of methyltransferase (MTase) target sites based on the introduction of a bioorthogonal propargyl group in vitro and in cells...
February 20, 2018: Angewandte Chemie
Kevin Tsai, David G Courtney, Bryan R Cullen
Polyomaviruses are a family of small DNA tumor viruses that includes several pathogenic human members, including Merkel cell polyomavirus, BK virus and JC virus. As is characteristic of DNA tumor viruses, gene expression in polyomaviruses is temporally regulated into an early phase, consisting of the viral regulatory proteins, and a late phase, consisting of the viral structural proteins. Previously, the late transcripts expressed by the prototypic polyomavirus simian virus 40 (SV40) were reported to contain several adenosines bearing methyl groups at the N6 position (m6A), although the precise location of these m6A residues, and their phenotypic effects, have not been investigated...
February 2018: PLoS Pathogens
Xianguang Zhao, Yang Chen, Qiqi Mao, Xiaoyun Jiang, Weiru Jiang, Jiajie Chen, Weijia Xu, Liang Zhong, Xu Sun
In China, hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer and the leading cause of cancer death in men, followed by lung and stomach cancer. There was an urgent need to identify novel prognostic biomarkers for HCC. We explored the expression pattern of m6A related proteins in HCC tissues by using TCGA in this study. We found that the m6A 'reader' YTHDF1 was significantly upregulated in HCC and was positive correlated with pathology stage. Kaplan-Meier analysis showed that Lower YTHDF1 expression level was associated with better survival of HCC patients...
2018: Cancer Biomarkers: Section A of Disease Markers
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