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https://www.readbyqxmd.com/read/28398475/fat-mass-and-obesity-associated-fto-protein-regulates-adult-neurogenesis
#1
Liping Li, Liqun Zang, Feiran Zhang, Junchen Chen, Hui Shen, Liqi Shu, Feng Liang, Chunyue Feng, Deng Chen, Huikang Tao, Tianlei Xu, Ziyi Li, Yunhee Kang, Hao Wu, Lichun Tang, Pumin Zhang, Peng Jin, Qiang Shu, Xuekun Li
Fat mass and obesity-associated gene (FTO) is a member of the Fe (II)- and oxoglutarate-dependent AlkB dioxygenase family and is linked to both obesity and intellectual disability. The role of FTO in neurodevelopment and neurogenesis, however, remains largely unknown. Here we show that FTO is expressed in adult neural stem cells and neurons and displays dynamic expression during postnatal neurodevelopment. The loss of FTO leads to decreased brain size and body weight. We find that FTO deficiency could reduce the proliferation and neuronal differentiation of adult neural stem cells in vivo, which leads to impaired learning and memory...
April 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28349456/illustrating-the-epitranscriptome-at-nucleotide-resolution-using-methylation-iclip-miclip
#2
Harry George, Jernej Ule, Shobbir Hussain
Next-generation sequencing technologies have enabled the transcriptome to be profiled at a previously unprecedented speed and depth. This yielded insights into fundamental transcriptomic processes such as gene transcription, RNA processing, and mRNA splicing. Immunoprecipitation-based transcriptomic methods such as individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) have also allowed high-resolution analysis of the RNA interactions of a protein of interest, thus revealing new regulatory mechanisms...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28349454/mapping-m-6-a-at-individual-nucleotide-resolution-using-crosslinking-and-immunoprecipitation-miclip
#3
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/28334903/n6-methyladenosine-alters-rna-structure-to-regulate-binding-of-a-low-complexity-protein
#4
Nian Liu, Katherine I Zhou, Marc Parisien, Qing Dai, Luda Diatchenko, Tao Pan
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and affects almost every stage of the mRNA life cycle. The YTH-domain proteins can specifically recognize m6A modification to control mRNA maturation, translation and decay. m6A can also alter RNA structures to affect RNA-protein interactions in cells. Here, we show that m6A increases the accessibility of its surrounding RNA sequence to bind heterogeneous nuclear ribonucleoprotein G (HNRNPG). Furthermore, HNRNPG binds m6A-methylated RNAs through its C-terminal low-complexity region, which self-assembles into large particles in vitro...
February 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28333151/fto-is-required-for-myogenesis-by-positively-regulating-mtor-pgc-1%C3%AE-pathway-mediated-mitochondria-biogenesis
#5
Xiaobo Wang, Ning Huang, Min Yang, Dandan Wei, Haoran Tai, Xiaojuan Han, Hui Gong, Jiao Zhou, Jianqiong Qin, Xiawei Wei, Honghan Chen, Tingting Fang, Hengyi Xiao
Global germ line loss of fat mass- and obesity-associated (FTO) gene results in both the reduction of fat mass and lean mass in mice. The role of FTO in adipogenesis has been proposed, however, that in myogenesis has not. Skeletal muscle is the main component of body lean mass, so its connection with FTO physiologic significance need to be clarified. Here, we assessed the impact of FTO on murine skeletal muscle differentiation by in vitro and in vivo experiments. We found that FTO expression increased during myoblasts differentiation, while the silence of FTO inhibited the differentiation; in addition, skeletal muscle development was impaired in skeletal muscle FTO-deficient mice...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332716/mir-124-and-mir-9-mediated-downregulation-of-hdac5-promotes-neurite-development-through-activating-mef2c-gpm6a-pathway
#6
Xi Gu, Congcong Fu, Lifang Lin, Shuhu Liu, Xiaohong Su, Aili Li, Qiaoqi Wu, Chunhong Jia, Peidong Zhang, Lu Chen, Xinhong Zhu, Xuemin Wang
The class IIa histone deacetylases (HDACs) play important roles in the central nervous system during diverse biological processes such as synaptic plasticity, axon regeneration, cell apoptosis, and neural differentiation. Although it is known that HDAC5 regulates neuronal differentiation, neither the physiological function nor the regulation of HDAC5 in neuronal differentiation is clear. Here, we identify HDAC5 as an inhibitor of neurite elongation and show that HDAC5 is regulated by the brain enriched microRNA miR-124 and miR-9...
March 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28275160/extracellular-signals-induce-glycoprotein-m6a-clustering-of-lipid-rafts-and-associated-signaling-molecules
#7
Atsuko Honda, Yasuyuki Ito, Kazuko Takahashi-Niki, Natsuki Matsushita, Motohiro Nozumi, Hidenori Tabata, Kosei Takeuchi, Michihiro Igarashi
Lipid raft domains, where sphingolipids and cholesterol are enriched, concentrate signaling molecules. To examine how signaling protein complexes are clustered in rafts, we focused on the functions of glycoprotein M6a (GPM6a), which is expressed at a high concentration in developing mouse neurons. Using imaging of lipid rafts, we found that GPM6a congregated in rafts in a GPM6a palmitoylation-dependent manner, thereby contributing to lipid raft clustering. In addition, we found that signaling proteins downstream of GPM6a, such as Rufy3, Rap2, and Tiam2/STEF, accumulated in lipid rafts in a GPM6a-dependent manner and were essential for laminin-dependent polarity during neurite formation in neuronal development...
April 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28267806/mrna-n6-methyladenosine-methylation-of-postnatal-liver-development-in-pig
#8
Shen He, Hong Wang, Rui Liu, Mengnan He, Tiandong Che, Long Jin, Lamei Deng, Shilin Tian, Yan Li, Hongfeng Lu, Xuewei Li, Zhi Jiang, Diyan Li, Mingzhou Li
N6-methyladenosine (m6A) is a ubiquitous reversible epigenetic RNA modification that plays an important role in the regulation of post-transcriptional protein coding gene expression. Liver is a vital organ and plays a major role in metabolism with numerous functions. Information concerning the dynamic patterns of mRNA m6A methylation during postnatal development of liver has been long overdue and elucidation of this information will benefit for further deciphering a multitude of functional outcomes of mRNA m6A methylation...
2017: PloS One
https://www.readbyqxmd.com/read/28247949/nsun2-mediated-m5c-methylation-and-mettl3-mettl14-mediated-m6a-methylation-cooperatively-enhance-p21-translation
#9
Qiu Li, Xiu Li, Hao Tang, Bin Jiang, Yali Dou, Myriam Gorospe, Wengong Wang
N6-methyladenosine (m6A) and m5C methylation are two major types of RNA methylation, but the impact of joint modifications on the same mRNA is unknown. Here, we show that in p21 3'UTR, NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Interestingly, methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2-mediated m5C and METTL3/METTL14-mediated m6A methylation synergistically enhance p21 expression at the translational level, leading to elevated expression of p21 in oxidative stress-induced cellular senescence...
March 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28138061/pseudouridine-and-n-6-methyladenosine-modifications-weaken-puf-protein-rna-interactions
#10
Pavanapuresan P Vaidyanathan, Ishraq AlSadhan, Dawn K Merriman, Hashim 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 non-coding 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 (m6A)- affect diverse cellular processes including mRNA splicing, localization, translation, and decay and modulate RNA structure...
January 30, 2017: RNA
https://www.readbyqxmd.com/read/28104805/microrna-145-modulates-n-6-methyladenosine-levels-by-targeting-the-3-untranslated-mrna-region-of-the-n-6-methyladenosine-binding-yth-domain-family-2-protein
#11
Zhe Yang, Jiong Li, Guoxing Feng, Shan Gao, Yuan Wang, Shuqin Zhang, Yunxia Liu, Lihong Ye, Yueguo Li, Xiaodong Zhang
N(6)-Methyladenosine (m(6)A) is a prevalent modification present in the mRNAs of higher eukaryotes. YTH domain family 2 (YTHDF2), an m(6)A "reader" protein, can recognize mRNA m(6)A sites to mediate mRNA degradation. However, the regulatory mechanism of YTHDF2 is poorly understood. To this end, we investigated the post-transcriptional regulation of YTHDF2. Bioinformatics analysis suggested that the microRNA miR-145 might target the 3'-untranslated region (3'-UTR) of YTHDF2 mRNA. The levels of miR-145 were negatively correlated with those of YTHDF2 mRNA in clinical hepatocellular carcinoma (HCC) tissues, and immunohistochemical staining revealed that YTHDF2 was closely associated with malignancy of HCC...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28063638/functional-dissection-of-the-m6a-rna-modification
#12
Brooke Huisman, Gabriel Manske, Stephen Carney, Sundeep Kalantry
No abstract text is available yet for this article.
February 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28052920/evolution-of-transcript-modification-by-n-6-methyladenosine-in-primates
#13
Lijia Ma, Boxuan Zhao, Kai Chen, Amber Thomas, Jigyasa H Tuteja, Xin He, Chuan He, Kevin P White
Phenotypic differences within populations and between closely related species are often driven by variation and evolution of gene expression. However, most analyses have focused on the effects of genomic variation at cis-regulatory elements such as promoters and enhancers that control transcriptional activity, and little is understood about the influence of post-transcriptional processes on transcript evolution. Post-transcriptional modification of RNA by N(6)-methyladenosine (m(6)A) has been shown to be widespread throughout the transcriptome, and this reversible mark can affect transcript stability and translation dynamics...
March 2017: Genome Research
https://www.readbyqxmd.com/read/28051309/chemical-modifications-to-rna-a-new-layer-of-gene-expression-regulation
#14
Jinghui Song, Chengqi Yi
The first chemical modification to RNA was discovered nearly 60 years ago; to date, more than 100 chemically distinct modifications have been identified in cellular RNA. With the recent development of novel chemical and/or biochemical methods, dynamic modifications to RNA have been identified in the transcriptome, including N(6)-methyladenosine (m(6)A), inosine (I), 5-methylcytosine (m(5)C), pseudouridine (Ψ), 5-hydroxymethylcytosine (hm(5)C), and N(1)-methyladenosine (m(1)A). Collectively, the multitude of RNA modifications are termed epitranscriptome, leading to the emerging field of epitranscriptomics...
January 12, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28027310/m6a-driver-identifying-context-specific-mrna-m6a-methylation-driven-gene-interaction-networks
#15
Song-Yao Zhang, Shao-Wu Zhang, Lian Liu, Jia Meng, Yufei Huang
As the most prevalent mammalian mRNA epigenetic modification, N6-methyladenosine (m6A) has been shown to possess important post-transcriptional regulatory functions. However, the regulatory mechanisms and functional circuits of m6A are still largely elusive. To help unveil the regulatory circuitry mediated by mRNA m6A methylation, we develop here m6A-Driver, an algorithm for predicting m6A-driven genes and associated networks, whose functional interactions are likely to be actively modulated by m6A methylation under a specific condition...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27997543/cell-cycle-constraints-and-environmental-control-of-local-dna-hypomethylation-in-%C3%AE-proteobacteria
#16
Silvia Ardissone, Peter Redder, Giancarlo Russo, Antonio Frandi, Coralie Fumeaux, Andrea Patrignani, Ralph Schlapbach, Laurent Falquet, Patrick H Viollier
Heritable DNA methylation imprints are ubiquitous and underlie genetic variability from bacteria to humans. In microbial genomes, DNA methylation has been implicated in gene transcription, DNA replication and repair, nucleoid segregation, transposition and virulence of pathogenic strains. Despite the importance of local (hypo)methylation at specific loci, how and when these patterns are established during the cell cycle remains poorly characterized. Taking advantage of the small genomes and the synchronizability of α-proteobacteria, we discovered that conserved determinants of the cell cycle transcriptional circuitry establish specific hypomethylation patterns in the cell cycle model system Caulobacter crescentus...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27825887/electrochemical-immunosensor-for-n6-methyladenosine-detection-in-human-cell-lines-based-on-biotin-streptavidin-system-and-silver-sio2-signal-amplification
#17
Huanshun Yin, Haiyan Wang, Wenjing Jiang, Yunlei Zhou, Shiyun Ai
N6-methyladenosine (m6A), a kind of RNA methylation form and important epigenetic event, plays crucial roles in many biological progresses. Thus it is essential to quantitatively detect m6A in complicated biological samples. Herein, a simple and sensitive electrochemical method was developed for m6A detection using N6-methyladenosine-5'-triphosphate (m6ATP) as detection target molecule. In this detection strategy, anti-m6A antibody was selected as m6A recognition and capture reagent, silver nanoparticles and amine-PEG3-biotin functionalized SiO2 nanospheres (Ag@SiO2) was prepared and used as signal amplification label, and phos-tag-biotin played a vital role of "bridge" to link m6ATP and Ag@SiO2 through the two forms of specific interaction between phosphate group of m6ATP and phos-tag, biotin and streptavidin, respectively...
April 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27793698/evidence-for-a-role-of-glycoprotein-m6a-in-dendritic-spine-formation-and-synaptogenesis
#18
Karina Formoso, Micaela D Garcia, Alberto C Frasch, Camila Scorticati
Neuronal glycoprotein M6a belongs to the tetraspan proteolipid protein (PLP) family. Mutations in GPM6A gene have been related to mental disorders like schizophrenia, bipolar disorders and claustrophobia. M6a is expressed mainly in neuronal cells of the central nervous system and it has been extensively related to neuronal plasticity. M6a induces neuritogenesis and axon/filopodium outgrowth; however its mechanism of action is still unresolved. We recently reported that the integrity of the transmembrane domains (TMDs) 2 and 4 are critical for M6a filopodia induction...
December 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27723837/rnamethpre-a-web-server-for-the-prediction-and-query-of-mrna-m6a-sites
#19
Shunian Xiang, Ke Liu, Zhangming Yan, Yaou Zhang, Zhirong Sun
N6-Methyladenosine (m6A) is the most common mRNA modification; it occurs in a wide range of taxon and is associated with many key biological processes. High-throughput experiments have identified m6A-peaks and sites across the transcriptome, but studies of m6A sites at the transcriptome-wide scale are limited to a few species and tissue types. Therefore, the computational prediction of mRNA m6A sites has become an important strategy. In this study, we integrated multiple features of mRNA (flanking sequences, local secondary structure information, and relative position information) and trained a SVM classifier to predict m6A sites in mammalian mRNA sequences...
2016: PloS One
https://www.readbyqxmd.com/read/27651356/rnas-containing-modified-nucleotides-fail-to-trigger-rig-i-conformational-changes-for-innate-immune-signaling
#20
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
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