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https://www.readbyqxmd.com/read/28934506/clip-seq-analysis-of-multi-mapped-reads-discovers-novel-functional-rna-regulatory-sites-in-the-human-transcriptome
#1
Zijun Zhang, Yi Xing
Crosslinking or RNA immunoprecipitation followed by sequencing (CLIP-seq or RIP-seq) allows transcriptome-wide discovery of RNA regulatory sites. As CLIP-seq/RIP-seq reads are short, existing computational tools focus on uniquely mapped reads, while reads mapped to multiple loci are discarded. We present CLAM (CLIP-seq Analysis of Multi-mapped reads). CLAM uses an expectation-maximization algorithm to assign multi-mapped reads and calls peaks combining uniquely and multi-mapped reads. To demonstrate the utility of CLAM, we applied it to a wide range of public CLIP-seq/RIP-seq datasets involving numerous splicing factors, microRNAs and m6A RNA methylation...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28869001/m6a-rna-methylation-a-new-hallmark-in-virus-host-interactions
#2
REVIEW
Michèle Brocard, Alessia Ruggieri, Nicolas Locker
The role of m6A methylation of RNA has remained elusive for decades, but recent technological advances are now allowing the mapping of the m6A methylation landscape at nucleotide level. This has spurred an explosion in our understanding of the role played by RNA epigenetics in RNA biology. m6A modifications have been tied to almost every aspect of the mRNA life cycle and it is now clear that RNA virus genomes are subject to m6A methylation. These modifications play various roles in the viral replication cycle...
September 2017: Journal of General Virology
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
#3
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/28851962/neural-glycoprotein-m6a-is-released-in-extracellular-vesicles-and-modulated-by-chronic-stressors-in-blood
#4
Melisa C Monteleone, Silvia C Billi, Marcela A Brocco, Alberto C Frasch
Membrane neuronal glycoprotein M6a is highly expressed in the brain and contributes to neural plasticity promoting neurite growth and spine and synapse formation. We have previously showed that chronic stressors alter hippocampal M6a mRNA levels in rodents and tree shrews. We now show that M6a glycoprotein can be detected in mouse blood. M6a is a transmembrane glycoprotein and, as such, unlikely to be free in blood. Here we demonstrate that, in blood, M6a is transported in extracellular vesicles (EVs). It is also shown that M6a-containing EVs are delivered from cultured primary neurons as well as from M6a-transfected COS-7 cells...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28841205/revisiting-gene-mutations-and-prognosis-of-ex-m6a-acute-erythroid-leukemia-with-regard-to-the-new-who-classification
#5
N Cervera, N Carbuccia, M-J Mozziconacci, J Adélaïde, S Garnier, A Guille, A Murati, M Chaffanet, N Vey, D Birnbaum, V Gelsi-Boyer
No abstract text is available yet for this article.
August 25, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28724534/m6aviewer-software-for-the-detection-analysis-and-visualization-of-n6-methyl-adenosine-peaks-from-m6a-seq-me-rip-sequencing-data
#6
Agne Antanaviciute, Belinda Baquero-Perez, Christopher M Watson, Sally M Harrison, Carolina Lascelles, Laura Crinnion, Alexander F Markham, David T Bonthron, Adrian Whitehouse, Ian M Carr
Recent methods for transcriptome-wide N6-methyl-adenosine(m6A) profiling have facilitated investigations into the RNA methylome and established m6A as a dynamic modification that has critical regulatory roles in gene expression and may play a role in human disease. However, bioinformatics resources available for the analysis of m6A sequencing data are still limited. Here, we describe m6aViewer - a cross-platform application for analysis and visualisation of m6A peaks from sequencing data. m6aViewer implements a novel m6A peak-calling algorithm that identifies high-confidence methylated residues with more precision than previously described approaches...
July 19, 2017: RNA
https://www.readbyqxmd.com/read/28655762/the-m-6-a-methyltransferase-ime4-epitranscriptionally-regulates-triacylglycerol-metabolism-and-vacuolar-morphology-in-haploid-yeast-cells
#7
COMPARATIVE STUDY
Pradeep Kumar Yadav, Ram Rajasekharan
N(6)-Methyladenosine (m(6)A) is among the most common modifications in eukaryotic mRNA. The role of yeast m(6)A methyltransferase, Ime4, in meiosis and sporulation in diploid strains is very well studied, but its role in haploid strains has remained unknown. Here, with the help of an immunoblotting strategy and Ime4-GFP protein localization studies, we establish the physiological role of Ime4 in haploid cells. Our data showed that Ime4 epitranscriptionally regulates triacylglycerol metabolism and vacuolar morphology through the long-chain fatty acyl-CoA synthetase Faa1, independently of the RNA methylation complex (MIS complex)...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28644387/rna-binding-proteins-and-genome-integrity
#8
REVIEW
Kensei Nishida, Yuki Kuwano, Tatsuya Nishikawa, Kiyoshi Masuda, Kazuhito Rokutan
Genome integrity can be threatened by various endogenous or exogenous events. To counteract these stressors, the DNA damage response network contributes to the prevention and/or repair of genomic DNA damage and serves an essential function in cellular survival. DNA binding proteins are involved in this network. Recently, several RNA-binding proteins (RBPs) that are recruited to DNA damage sites have been shown to be direct players in the prevention or repair of DNA damage. In addition, non-coding RNAs, themselves, are involved in the RNA-mediated DNA repair system...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28637404/role-of-dna-and-rna-n6-adenine-methylation-in-regulating-stem-cell-fate
#9
Yunshu Wu, Chenchen Zhou, Quan Yuan
Epigenetic modifications have been evidenced to participate in eukaryotic stem cell fate decision. Among the most studied, 5-methylcytosine (m5C) and its derivatives are well-established epigenetic codes that play important roles in stem cell pluripotency and differentiation. Based on improved detection techniques, recent studies have succeeded in defining N6-adenine methylation (m6A) in eukaryotic DNA and RNA. The abundant m6A methylation in RNA was shown to be involved in multiple cellular metabolisms while the presence and functional potential of DNA m6A methylation in different species advanced our knowledge in the m6A-mediated biological processes...
June 21, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28611253/n-6-methyladenosine-is-required-for-the-hypoxic-stabilization-of-specific-mrnas
#10
Nate J Fry, Brittany A Law, Olga R Ilkayeva, Christopher L Holley, Kyle D Mansfield
Post-transcriptional regulation of mRNA during oxygen deprivation, or hypoxia, can affect the survivability of cells. Hypoxia has been shown to increase stability of a subset of ischemia-related mRNAs, including VEGF. RNA binding proteins and miRNAs have been identified as important for post-transcriptional regulation of individual mRNAs, but corresponding mechanisms that regulate global stability are not well understood. Recently, mRNA modification by N(6)-methyladenosine (m(6)A) has been shown to be involved in post-transcriptional regulation processes including mRNA stability and promotion of translation, but the role of m(6)A in the hypoxia response is unknown...
September 2017: RNA
https://www.readbyqxmd.com/read/28591780/position-dependent-effects-of-regioisomeric-methylated-adenine-and-guanine-ribonucleosides-on-translation
#11
Changjun You, Xiaoxia Dai, Yinsheng Wang
Reversible methylation of the N6 or N1 position of adenine in RNA has recently been shown to play significant roles in regulating the functions of RNA. RNA can also be alkylated upon exposure to endogenous and exogenous alkylating agents. Here we examined how regio-specific methylation at the hydrogen bonding edge of adenine and guanine in mRNA affects translation. When situated at the third codon position, the methylated nucleosides did not compromise the speed or accuracy of translation under most circumstances...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28549193/label-free-direct-localization-and-relative-quantitation-of-the-rna-nucleobase-methylations-m6a-m5c-m3u-and-m5u-by-top-down-mass-spectrometry
#12
Heidelinde Glasner, Christian Riml, Ronald Micura, Kathrin Breuker
Nucleobase methylations are ubiquitous posttranscriptional modifications of ribonucleic acids (RNA) that can substantially increase the structural diversity of RNA in a highly dynamic fashion with implications for gene expression and human disease. However, high throughput, deep sequencing does not generally provide information on posttranscriptional modifications (PTMs). A promising alternative approach for the characterization of PTMs, i.e. their identification, localization, and relative quantitation, is top-down mass spectrometry (MS)...
July 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28494721/m6a-modification-and-implications-for-micrornas
#13
Ayse Elif Erson-Bensan, Oguzhan Begik
RNA is chemically modified with over 100 distinct reactions. Among these reactions, methylation is probably the most extensively studied modification on the RNA molecule. Studies suggest methylation of Adenine residues (m6A) to be widespread in the transcriptome with potentially important roles in biological processes. Here, we review recent literature on m6A modification and potential implications for microRNA (miRNA) mediated gene expression regulation. These implications involve miRNA biogenesis, mRNA-miRNA interactions and m6A target selection...
May 10, 2017: MicroRNA
https://www.readbyqxmd.com/read/28469844/the-roles-of-micrornas-in-regulation-of-mammalian-spermatogenesis
#14
REVIEW
Xiaoxu Chen, Xueliang Li, Jiayin Guo, Pengfei Zhang, Wenxian Zeng
Mammalian spermatogenesis contains three continuous and organized processes, by which spermatogonia undergo mitosis and differentiate to spermatocytes, follow on meiosis to form haploid spermatids and ultimately transform into spermatozoa. These processes require an accurately, spatially and temporally regulated gene expression patterns. The microRNAs are a novel class of post-transcriptional regulators. Cumulating evidences have demonstrated that microRNAs are expressed in a cell-specific or stage-specific manner during spermatogenesis...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28453518/lc-ms-ms-quantitative-analysis-reveals-the-association-between-fto-and-dna-methylation
#15
Yuting Zhu, Guangyu Zhou, Xuebin Yu, Qiang Xu, Kai Wang, Dan Xie, Qingkai Yang, Lina Wang
Fat mass and obesity-associated protein (FTO) is α-ketoglutarate-dependent dioxygenase and responsible for demethylating N6-methyladenosine (m6A) in mRNA, 3-methylthymine (m3T) in single-stranded DNA (ssDNA) and 3-methyluracil (m3U) in single-stranded RNA (ssRNA). Its other function remains unknown but thousands of mammalian DNA show 5-methyl-2'-deoxycytidine (5mdC) modification and 5mdC demethylases are required for mammalian energy homeostasis and fertility. Here, we aimed to confirm whether FTO proteins can demethylate 5mdC in DNA...
2017: PloS One
https://www.readbyqxmd.com/read/28398475/fat-mass-and-obesity-associated-fto-protein-regulates-adult-neurogenesis
#16
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...
July 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28349456/illustrating-the-epitranscriptome-at-nucleotide-resolution-using-methylation-iclip-miclip
#17
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
#18
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
#19
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...
June 2, 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
#20
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
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