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Posttranscriptional modification

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https://www.readbyqxmd.com/read/29325627/epigenetic-mechanisms-underlying-nervous-system-diseases
#1
Irfan A Qureshi, Mark F Mehler
Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29279410/alkbh5-dependent-m6a-demethylation-controls-splicing-and-stability-of-long-3-utr-mrnas-in-male-germ-cells
#2
Chong Tang, Rachel Klukovich, Hongying Peng, Zhuqing Wang, Tian Yu, Ying Zhang, Huili Zheng, Arne Klungland, Wei Yan
N6-methyladenosine (m6A) represents one of the most common RNA modifications in eukaryotes. Specific m6A writer, eraser, and reader proteins have been identified. As an m6A eraser, ALKBH5 specifically removes m6A from target mRNAs and inactivation of Alkbh5 leads to male infertility in mice. However, the underlying molecular mechanism remains unknown. Here, we report that ALKBH5-mediated m6A erasure in the nuclei of spermatocytes and round spermatids is essential for correct splicing and the production of longer 3'-UTR mRNAs, and failure to do so leads to aberrant splicing and production of shorter transcripts with elevated levels of m6A that are rapidly degraded...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29273296/an-archaeal-aminoacyl-trna-synthetase-complex-for-improved-substrate-quality-control
#3
Ana Crnković, Mirela Čavužić, Vlatka Godinić-Mikulčić, Gregor Anderluh, Ivana Weygand-Đurašević, Ita Gruić-Sovulj
Aminoacyl-tRNA synthetases (aaRS) decode genetic information by coupling tRNAs with cognate amino acids. In the archaeon Methanothermobacter thermautotrophicus arginyl- and seryl-tRNA synthetase (ArgRS and SerRS, respectively) form a complex which enhances serylation and facilitates tRNASer recycling through its association with the ribosome. Yet, the way by which complex formation participates in Arg-tRNAArg synthesis is still unresolved. Here we utilized pull down and surface plasmon resonance experiments with truncated ArgRS variants to demonstrate that ArgRS uses its N-terminal domain to establish analogous interactions with both SerRS and cognate tRNAArg, providing a rationale for the lack of detectable SerRS•[ArgRS•tRNAArg] complex...
December 19, 2017: Biochimie
https://www.readbyqxmd.com/read/29239917/natural-compounds-as-epigenetic-regulators-of-human-dendritic-cell-mediated-immune-function
#4
Sheefa Mirza, Kanisha Shah, Shanaya Patel, Nayan Jain, Rakesh Rawal
Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and are poised to capture antigen, migrate to draining lymphoid organs, and postmaturation process. Recent evidences have suggested that tumor microenvironment has an effect on DCs by inactivating various components of the immune system responsible for tumor clearance, eventually leading to tumorigenesis. This inactivation is owed to the epigenetic modifications [ie, microRNA (miRNA)] at the posttranscriptional level, thus regulating the differentiation patterns and functional behavior of DCs...
December 12, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29228327/most-m6a-rna-modifications-in-protein-coding-regions-are-evolutionarily-unconserved-and-likely-nonfunctional
#5
Zhen Liu, Jianzhi Zhang
Methylation of the adenosine base at the nitrogen-6 position (m6A) is the most prevalent internal posttranscriptional modification of mRNAs in many eukaryotes. Despite the rapid progress in the transcriptome-wide mapping of m6As, identification of proteins responsible for writing, reading, and erasing m6As, and elucidation of m6A functions in splicing, RNA stability, translation, and other processes, it is unknown whether most observed m6A modifications are functional. To address this question, we respectively analyze the evolutionary conservation of yeast and human m6As in protein-coding regions...
December 8, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29212285/bancr-a-novel-oncogenic-long-non-coding-rna-in-human-cancers
#6
REVIEW
Yifan Zou, Jianfa Li, Yincong Chen, Huizhong Xiao, Fuyou Zhang, Dan Yu, Kewang Luo
Long non-coding RNAs account for large proportion of non-coding transcripts in human genomes. Though they lack of open reading framework and cannot encode protein, they can control endogenous gene expression though regulating cell life activities. They serve as transcriptional modulator, posttranscriptional processor, chromatin remodeler and splicing regulator during the process of gene modification. Moreover, long non-coding RNAs were regarded as potential tumor markers for cancer diagnosis and prognosis. BANCR was identified as a cancer-promoting long non-coding RNA in melanoma tissues...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29167681/mir-200b-downregulates-cftr-during-hypoxia-in-human-lung-epithelial-cells
#7
Sylwia Bartoszewska, Wojciech Kamysz, Bogdan Jakiela, Marek Sanak, Jarosław Króliczewski, Zsuzsa Bebok, Rafal Bartoszewski, James F Collawn
Background: Hypoxic conditions induce the expression of hypoxia-inducible factors (HIFs) that allow cells to adapt to the changing conditions and alter the expression of a number of genes including the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a low abundance mRNA in airway epithelial cells even during normoxic conditions, but during hypoxia its mRNA expression decreases even further. Methods: In the current studies, we examined the kinetics of hypoxia-induced changes in CFTR mRNA and protein levels in two human airway epithelial cell lines, Calu-3 and 16HBE14o-, and in normal primary bronchial epithelial cells...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/29167375/loss-of-apobec1-rna-editing-function-in-microglia-exacerbates-age-related-cns-pathophysiology
#8
Daniel C Cole, Youngcheul Chung, Khatuna Gagnidze, Kaitlyn H Hajdarovic, Violeta Rayon-Estrada, Dewi Harjanto, Benedetta Bigio, Judit Gal-Toth, Teresa A Milner, Bruce S McEwen, F Nina Papavasiliou, Karen Bulloch
Microglia (MG), a heterogeneous population of phagocytic cells, play important roles in central nervous system (CNS) homeostasis and neural plasticity. Under steady-state conditions, MG maintain homeostasis by producing antiinflammatory cytokines and neurotrophic factors, support myelin production, and remove synapses and cellular debris, as well as participating in "cross-correction," a process that supplies neurons with key factors for executing autophagy-lysosomal function. As sentinels for the immune system, MG also detect "danger" signals (pathogenic or traumatic insult), become activated, produce proinflammatory cytokines, and recruit monocytes and dendritic cells to the site of damage through a breached blood-brain barrier or via brain lymphatics...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29167373/epitranscriptomic-profiling-across-cell-types-reveals-associations-between-apobec1-mediated-rna-editing-gene-expression-outcomes-and-cellular-function
#9
Violeta Rayon-Estrada, Dewi Harjanto, Claire E Hamilton, Yamina A Berchiche, Emily Conn Gantman, Thomas P Sakmar, Karen Bulloch, Khatuna Gagnidze, Sheila Harroch, Bruce S McEwen, F Nina Papavasiliou
Epitranscriptomics refers to posttranscriptional alterations on an mRNA sequence that are dynamic and reproducible, and affect gene expression in a similar way to epigenetic modifications. However, the functional relevance of those modifications for the transcript, the cell, and the organism remain poorly understood. Here, we focus on RNA editing and show that Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-1 (APOBEC1), together with its cofactor RBM47, mediates robust editing in different tissues...
November 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29165544/rna-methylation-and-diseases-experimental-results-databases-web-servers-and-computational-models
#10
Xing Chen, Ya-Zhou Sun, Hui Liu, Lin Zhang, Jian-Qiang Li, Jia Meng
Ribonucleic acid (RNA) methylation is a type of posttranscriptional modifications occurring in all kingdoms of life. It is strongly related to important biological process, thus making it linked to a number of human diseases. Owing to the development of high-throughput sequencing technology, plenty of achievement had been obtained in RNA methylation research recently. Meanwhile, various computational models have been developed to analyze and mining increasing RNA methylation data. In this review, we first made a brief introduction about eight types of most popular RNA methylation, the biological functions of RNA methylation, the relationship between RNA methylation and disease and five important RNA methylation-related diseases...
November 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29143920/distinguishing-the-disease-associated-snps-based-on-composition-frequency-analysis
#11
Wenling Li, Menglong Li, Xuemei Pu, Yanzhi Guo
Single-nucleotide polymorphism (SNP) is a basical variation in genome. When SNPs occur at the binding sites of microRNA, they can influence the binding efficiency, cause a fluctuation of the mRNA in vivo, and thus arouse posttranscriptional level abnormality. Therefore, SNP has a strong correlation with diseases. Although enormous SNPs have been experimentally identified, only a tiny proportion of them are truly disease-associated SNPs (dSNPs) that relate to microRNA modification and then are involved in disease causing process...
November 16, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/29130189/identifying-the-m-6-a-methylome-by-affinity-purification-and-sequencing
#12
Phillip J Hsu, Chuan He
N (6)-methyladenosine (m(6)A) is the most abundant internal modification in eukaryotic mRNA, and is newly emerging as a key posttranscriptional mRNA regulator. Recent research has uncovered insight into the location and function of m(6)A sites on a large scale, in part due to the transcriptome-wide identification of m(6)A sites by high-throughput sequencing (m(6)A-seq). Here, we present a protocol for m(6)A-seq, which maps the m(6)A methylome by affinity purification and sequencing.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29111692/fingerprints-of-modified-rna-bases-from-deep-sequencing-profiles
#13
Anna M Kietrys, Willem A Velema, Eric T Kool
Posttranscriptional modifications of RNA bases are not only found in many noncoding RNAs but have also recently been identified in coding (messenger) RNAs as well. They require complex and laborious methods to locate, and many still lack methods for localized detection. Here we test the ability of next-generation sequencing (NGS) to detect and distinguish between ten modified bases in synthetic RNAs. We compare ultradeep sequencing patterns of modified bases, including miscoding, insertions and deletions (indels), and truncations, to unmodified bases in the same contexts...
November 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29073095/broad-role-for-ybx1-in-defining-the-small-noncoding-rna-composition-of-exosomes
#14
Matthew J Shurtleff, Jun Yao, Yidan Qin, Ryan M Nottingham, Morayma M Temoche-Diaz, Randy Schekman, Alan M Lambowitz
RNA is secreted from cells enclosed within extracellular vesicles (EVs). Defining the RNA composition of EVs is challenging due to their coisolation with contaminants, lack of knowledge of the mechanisms of RNA sorting into EVs, and limitations of conventional RNA-sequencing methods. Here we present our observations using thermostable group II intron reverse transcriptase sequencing (TGIRT-seq) to characterize the RNA extracted from HEK293T cell EVs isolated by flotation gradient ultracentrifugation and from exosomes containing the tetraspanin CD63 further purified from the gradient fractions by immunoisolation...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29042505/binding-synergy-as-an-essential-step-for-trna-editing-and-modification-enzyme-co-dependence-in-trypanosoma-brucei
#15
Katherine Mary McKenney, Mary Anne T Rubio, Juan D Alfonzo
Transfer RNAs acquire a variety of naturally occurring chemical modifications during their maturation; these fine-tune their structure and decoding properties in a manner critical for protein synthesis. We recently reported that in the eukaryotic parasite, Trypanosoma brucei, a methylation and deamination event are unexpectedly interconnected, whereby the tRNA adenosine deaminase (TbADAT2/3) and the 3-methylcytosine methyltransferase (TbTrm140) strictly rely on each other for activity, leading to formation of m(3)C and m(3)U at position 32 in several tRNAs...
October 17, 2017: RNA
https://www.readbyqxmd.com/read/29040360/elucidating-the-editome-bioinformatics-approaches-for-rna-editing-detection
#16
Maria Angela Diroma, Loredana Ciaccia, Graziano Pesole, Ernesto Picardi
RNA editing is a widespread co/posttranscriptional mechanism affecting primary RNAs by specific nucleotide modifications, which plays relevant roles in molecular processes including regulation of gene expression and/or the processing of noncoding RNAs. In recent years, the detection of editing sites has been improved through the availability of high-throughput RNA sequencing (RNA-Seq) technologies. Accurate bioinformatics pipelines are essential for the analysis of next-generation sequencing (NGS) data to ensure the correct identification of edited sites...
October 11, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28984054/rna-uridylation-a-key-posttranscriptional-modification-shaping-the-coding-and-noncoding-transcriptome
#17
REVIEW
Caroline De Almeida, Hélène Scheer, Hélène Zuber, Dominique Gagliardi
RNA uridylation is a potent and widespread posttranscriptional regulator of gene expression. RNA uridylation has been detected in a range of eukaryotes including trypanosomes, animals, plants, and fungi, but with the noticeable exception of budding yeast. Virtually all classes of eukaryotic RNAs can be uridylated and uridylation can also tag viral RNAs. The untemplated addition of a few uridines at the 3' end of a transcript can have a decisive impact on RNA's fate. In rare instances, uridylation is an intrinsic step in the maturation of noncoding RNAs like for the U6 spliceosomal RNA or mitochondrial guide RNAs in trypanosomes...
October 5, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28968025/-the-role-of-interactions-of-transposons-with-epigenetic-factors-in-the-aging-process
#18
R N Mustafin, E K Khusnutdinova
The review considers modern theories of aging mechanisms and data on epigenetic regulation of ontogenesis. Transposons may be the material bases of the epigenetic control system, their movements affect the differentiation of cells and can cause genomic instability. Control systems aimed at protecting against foreign DNA (splicing machine, microRNA processing) became the basis of regulatory networks of genomes underlying cell differentiation. Transposon sequences are the basis for non-coding RNAs that suppress the expression of the transposons themselves and protein-coding genes at the posttranscriptional level, as well as by altering the activity of methyltransferases and modifying the histone modification...
2017: Advances in Gerontology, Uspekhi Gerontologii
https://www.readbyqxmd.com/read/28917036/selenocysteine-trna-ser-sec-the-central-component-of-selenoprotein-biosynthesis-isolation-identification-modification-and-sequencing
#19
Bradley A Carlson, Byeong Jae Lee, Petra A Tsuji, Paul R Copeland, Ulrich Schweizer, Vadim N Gladyshev, Dolph L Hatfield
The selenocysteine (Sec) tRNA([Ser]Sec) population consists of two isoforms that differ from each other by a single 2'-O-methylribosyl moiety at position 34 (Um34). These two isoforms, which are encoded in a single gene, Trsp, and modified posttranscriptionally, are involved individually in the synthesis of two subclasses of selenoproteins, designated housekeeping and stress-related selenoproteins. Techniques used in obtaining these isoforms for their characterization include extraction of RNA from mammalian cells and tissues, purifying the tRNA([Ser]Sec) population by one or more procedures, and finally resolving the two isoforms from each other...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28914256/mettl3-mettl14-mediated-mrna-n6-methyladenosine-modulates-murine-spermatogenesis
#20
Zhen Lin, Phillip J Hsu, Xudong Xing, Jianhuo Fang, Zhike Lu, Qin Zou, Ke-Jia Zhang, Xiao Zhang, Yuchuan Zhou, Teng Zhang, Youcheng Zhang, Wanlu Song, Guifang Jia, Xuerui Yang, Chuan He, Ming-Han Tong
Spermatogenesis is a differentiation process during which diploid spermatogonial stem cells (SSCs) produce haploid spermatozoa. This highly specialized process is precisely controlled at the transcriptional, posttranscriptional, and translational levels. Here we report that N6-methyladenosine (m6A), an epitranscriptomic mark regulating gene expression, plays essential roles during spermatogenesis. We present comprehensive m6A mRNA methylomes of mouse spermatogenic cells from five developmental stages: undifferentiated spermatogonia, type A1 spermatogonia, preleptotene spermatocytes, pachytene/diplotene spermatocytes, and round spermatids...
October 2017: Cell Research
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