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https://www.readbyqxmd.com/read/28104805/microrna-145-modulates-n6-methyladenosine-levels-by-targeting-the-3-untranslated-mrna-region-of-the-n6-methyladenosine-binding-yth-domain-family-2-protein
#1
Zhe Yang, Jiong Li, Guoxing Feng, Shan Gao, Yuan Wang, Shuqin Zhang, Yunxia Liu, Lihong Ye, Yueguo Li, Xiaodong Zhang
N6 methyladenosine (m6A) is a prevalent modification present in the mRNAs of higher eukaryotes. YTH domain family 2 (YTHDF2), an m6A reader protein, can recognize mRNA m6A 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...
January 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28063638/functional-dissection-of-the-m6a-rna-modification
#2
Brooke Huisman, Gabriel Manske, Stephen Carney, Sundeep Kalantry
No abstract text is available yet for this article.
January 4, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28052920/evolution-of-transcript-modification-by-n6-methyladenosine-in-primates
#3
Lijia Ma, Boxuan Zhao, Kai Chen, Amber Thomas, Jigyasa H Tuteja, Xin He, Chuan He, Kevin White
Phenotypic differences within populations and between closely related species are often driven by variation and evolution of gene expression (King and Wilson 1975; Romero et al. 2012; Villar et al. 2014). 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 N6-methyladenosine (m6A) has been shown to be widespread throughout the transcriptome (Desrosiers et al...
January 4, 2017: Genome Research
https://www.readbyqxmd.com/read/28051309/chemical-modifications-to-rna-a-new-layer-of-gene-expression-regulation
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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/27613873/n6-methyladenosine-sequencing-highlights-the-involvement-of-mrna-methylation-in-oocyte-meiotic-maturation-and-embryo-development-by-regulating-translation-in-xenopus-laevis
#12
Shu-Tao Qi, Jun-Yu Ma, Zhen-Bo Wang, Lei Guo, Yi Hou, Qing-Yuan Sun
During the oogenesis of Xenopus laevis, oocytes accumulate maternal materials for early embryo development. As the transcription activity of the oocyte is silenced at the fully grown stage and the global genome is reactivated only by the mid-blastula embryo stage, the translation of maternal mRNAs accumulated during oocyte growth should be accurately regulated. Previous evidence has illustrated that the poly(A) tail length and RNA binding elements mediate RNA translation regulation in the oocyte. Recently, RNA methylation has been found to exist in various systems...
October 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27590511/hypoxia-inducible-factors-regulate-pluripotency-factor-expression-by-znf217-and-alkbh5-mediated-modulation-of-rna-methylation-in-breast-cancer-cells
#13
Chuanzhao Zhang, Wanqing Iris Zhi, Haiquan Lu, Debangshu Samanta, Ivan Chen, Edward Gabrielson, Gregg L Semenza
Exposure of breast cancer cells to hypoxia increases the percentage of breast cancer stem cells (BCSCs), which are required for tumor initiation and metastasis, and this response is dependent on the activity of hypoxia-inducible factors (HIFs). We previously reported that exposure of breast cancer cells to hypoxia induces the ALKBH5-mediated demethylation of N6-methyladenosine (m6A) in NANOG mRNA leading to increased expression of NANOG, which is a pluripotency factor that promotes BCSC specification. Here we report that exposure of breast cancer cells to hypoxia also induces ZNF217-dependent inhibition of m6A methylation of mRNAs encoding NANOG and KLF4, which is another pluripotency factor that mediates BCSC specification...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27580720/novel-m4c-modification-in-type-i-restriction-modification-systems
#14
Richard D Morgan, Yvette A Luyten, Samuel A Johnson, Emily M Clough, Tyson A Clark, Richard J Roberts
We identify a new subgroup of Type I Restriction-Modification enzymes that modify cytosine in one DNA strand and adenine in the opposite strand for host protection. Recognition specificity has been determined for ten systems using SMRT sequencing and each recognizes a novel DNA sequence motif. Previously characterized Type I systems use two identical copies of a single methyltransferase (MTase) subunit, with one bound at each half site of the specificity (S) subunit to form the MTase. The new m4C-producing Type I systems we describe have two separate yet highly similar MTase subunits that form a heterodimeric M1M2S MTase...
August 31, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27578426/consequences-of-excessive-plasticity-in-the-hippocampus-induced-by-perinatal-asphyxia
#15
G E Saraceno, L G Caceres, L R Guelman, R Castilla, L D Udovin, M H Ellisman, M A Brocco, F Capani
Perinatal asphyxia (PA) is one of the most frequent risk factors for several neurodevelopmental disorders (NDDs) of presumed multifactorial etiology. Dysfunction of neuronal connectivity is thought to play a central role in the pathophysiology of NDDs. Because underlying causes of some NDDs begin before/during birth, we asked whether this clinical condition might affect accurate establishment of neural circuits in the hippocampus as a consequence of disturbed brain plasticity. We used a murine model that mimics the pathophysiological processes of perinatal asphyxia...
August 27, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27552763/targetm6a-identifying-n-6-methyladenosine-sites-from-rna-sequences-via-position-specific-nucleotide-propensities-and-a-support-vector-machine
#16
Guang-Qing Li, Zi Liu, Hong-Bin Shen, Dong-Jun Yu
As one of the most ubiquitous post-transcriptional modifications of RNA, N(6)-methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i...
October 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/27307641/a-novel-algorithm-for-calling-mrna-m6a-peaks-by-modeling-biological-variances-in-merip-seq-data
#17
Xiaodong Cui, Jia Meng, Shaowu Zhang, Yidong Chen, Yufei Huang
MOTIVATION: N(6)-methyl-adenosine (m(6)A) is the most prevalent mRNA methylation but precise prediction of its mRNA location is important for understanding its function. A recent sequencing technology, known as Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq), has been developed for transcriptome-wide profiling of m(6)A. We previously developed a peak calling algorithm called exomePeak. However, exomePeak over-simplifies data characteristics and ignores the reads' variances among replicates or reads dependency across a site region...
June 15, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27293216/improving-n-6-methyladenosine-site-prediction-with-heuristic-selection-of-nucleotide-physical-chemical-properties
#18
Ming Zhang, Jia-Wei Sun, Zi Liu, Ming-Wu Ren, Hong-Bin Shen, Dong-Jun Yu
N(6)-methyladenosine (m(6)A) is one of the most common and abundant post-transcriptional RNA modifications found in viruses and most eukaryotes. m(6)A plays an essential role in many vital biological processes to regulate gene expression. Because of its widespread distribution across the genomes, the identification of m(6)A sites from RNA sequences is of significant importance for better understanding the regulatory mechanism of m(6)A. Although progress has been achieved in m(6)A site prediction, challenges remain...
September 1, 2016: Analytical Biochemistry
https://www.readbyqxmd.com/read/27269119/discriminating-self-and-non-self-by-rna-roles-for-rna-structure-misfolding-and-modification-in-regulating-the-innate-immune-sensor-pkr
#19
Chelsea M Hull, Philip C Bevilacqua
Pathogens are recognized by the innate immune system in part via their unique and complex RNA signatures. A key sensor in human innate immunity is the RNA-activated protein kinase, protein kinase R (PKR), which has two double-stranded RNA (dsRNA) binding motifs (dsRBMs) at its N-terminus. Early studies described PKR as being activated potently by long stretches of perfect dsRNA, a signature typical of viruses. More recently, we and others have found that PKR is also activated by RNAs having structural defects such as bulges and internal loops...
June 21, 2016: Accounts of Chemical Research
https://www.readbyqxmd.com/read/27249342/recent-advances-in-dynamic-m6a-rna-modification
#20
REVIEW
Guangchao Cao, Hua-Bing Li, Zhinan Yin, Richard A Flavell
The identification of m(6)A demethylases and high-throughput sequencing analysis of methylated transcriptome corroborated m(6)A RNA epigenetic modification as a dynamic regulation process, and reignited its investigation in the past few years. Many basic concepts of cytogenetics have been revolutionized by the growing understanding of the fundamental role of m(6)A in RNA splicing, degradation and translation. In this review, we summarize typical features of methylated transcriptome in mammals, and highlight the 'writers', 'erasers' and 'readers' of m(6)A RNA modification...
April 2016: Open Biology
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