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Rna editing

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https://www.readbyqxmd.com/read/27926534/irna-ai-identifying-the-adenosine-to-inosine-editing-sites-in-rna-sequences
#1
Wei Chen, Pengmian Feng, Hui Yang, Hui Ding, Hao Lin, Kuo-Chen Chou
Catalyzed by adenosine deaminase (ADAR), the adenosine to inosine (A-to-I) editing in RNA is not only involved in various important biological processes, but also closely associated with a series of major diseases. Therefore, knowledge about the A-to-I editing sites in RNA is crucially important for both basic research and drug development. Given an uncharacterized RNA sequence that contains many adenosine (A) residues, can we identify which one of them can be of A-to-I editing, and which one cannot? Unfortunately, so far no computational method whatsoever has been developed to address such an important problem based on the RNA sequence information alone...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27918548/multiplex-gene-editing-by-crispr-cpf1-using-a-single-crrna-array
#2
Bernd Zetsche, Matthias Heidenreich, Prarthana Mohanraju, Iana Fedorova, Jeroen Kneppers, Ellen M DeGennaro, Nerges Winblad, Sourav R Choudhury, Omar O Abudayyeh, Jonathan S Gootenberg, Wen Y Wu, David A Scott, Konstantin Severinov, John van der Oost, Feng Zhang
Targeting of multiple genomic loci with Cas9 is limited by the need for multiple or large expression constructs. Here we show that the ability of Cpf1 to process its own CRISPR RNA (crRNA) can be used to simplify multiplexed genome editing. Using a single customized CRISPR array, we edit up to four genes in mammalian cells and three in the mouse brain, simultaneously.
December 5, 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/27911851/inherited-variants-affecting-rna-editing-may-contribute-to-ovarian-cancer-susceptibility-results-from-a-large-scale-collaboration
#3
Jennifer B Permuth, Brett Reid, Madalene Earp, Y Ann Chen, Alvaro N A Monteiro, Zhihua Chen, Aocs Study Group, Georgia Chenevix-Trench, Peter A Fasching, Matthias W Beckmann, Diether Lambrechts, Adriaan Vanderstichele, Els Van Niewenhuyse, Ignace Vergote, Mary Anne Rossing, Jennifer Anne Doherty, Jenny Chang-Claude, Kirsten Moysich, Kunle Odunsi, Marc T Goodman, Yurii B Shvetsov, Lynne R Wilkens, Pamela J Thompson, Thilo Dörk, Natalia Bogdanova, Ralf Butzow, Heli Nevanlinna, Liisa Pelttari, Arto Leminen, Francesmary Modugno, Robert P Edwards, Roberta B Ness, Joseph Kelley, Florian Heitz, Beth Karlan, Jenny Lester, Susanne K Kjaer, Allan Jensen, Graham Giles, Michelle Hildebrandt, Dong Liang, Karen H Lu, Xifeng Wu, Douglas A Levine, Maria Bisogna, Andrew Berchuck, Daniel W Cramer, Kathryn L Terry, Shelley S Tworoger, Elizabeth M Poole, Elisa V Bandera, Brooke Fridley, Julie Cunningham, Stacey J Winham, Sara H Olson, Irene Orlow, Line Bjorge, Lambertus A Kiemeney, Leon Massuger, Tanja Pejovic, Melissa Moffitt, Nhu Le, Linda S Cook, Angela Brooks-Wilson, Linda E Kelemen, Jacek Gronwald, Jan Lubinski, Nicolas Wentzensen, Louise A Brinton, Jolanta Lissowska, Hanna Yang, Estrid Hogdall, Claus Hogdall, Lene Lundvall, Paul D P Pharoah, Honglin Song, Ian Campbell, Diana Eccles, Iain McNeish, Alice Whittemore, Valerie McGuire, Weiva Sieh, Joseph Rothstein, Catherine M Phelan, Harvey Risch, Steven Narod, John McLaughlin, Hoda Anton-Culver, Argyrios Ziogas, Usha Menon, Simon Gayther, Susan J Ramus, Aleksandra Gentry-Maharaj, Celeste Leigh Pearce, Anna H Wu, Jolanta Kupryjanczyk, Agnieszka Dansonka-Mieszkowska, Joellen M Schildkraut, Jin Q Cheng, Ellen L Goode, Thomas A Sellers
RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single nucleotide polymorphisms (SNPs) in ADAR genes modify EOC susceptibility, potentially by altering ovarian tissue gene expression. Using directly genotyped and imputed data from 10,891 invasive EOC cases and 21,693 controls, we evaluated the associations of 5,303 SNPs in ADAD1, ADAR, ADAR2, ADAR3, and SND1...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910942/improved-bi-allelic-modification-of-a-transcriptionally-silent-locus-in-patient-derived-ipsc-by-cas9-nickase
#4
Reto Eggenschwiler, Mohsen Moslem, Mariane Serra Fráguas, Melanie Galla, Oliver Papp, Maximilian Naujock, Ines Fonfara, Ingrid Gensch, Annabell Wähner, Abbas Beh-Pajooh, Claudio Mussolino, Marcel Tauscher, Doris Steinemann, Florian Wegner, Susanne Petri, Axel Schambach, Emmanuelle Charpentier, Toni Cathomen, Tobias Cantz
Homology directed repair (HDR)-based genome editing via selectable long flanking arm donors can be hampered by local transgene silencing at transcriptionally silent loci. Here, we report efficient bi-allelic modification of a silent locus in patient-derived hiPSC by using Cas9 nickase and a silencing-resistant donor construct that contains an excisable selection/counter-selection cassette. To identify the most active single guide RNA (sgRNA)/nickase combinations, we employed a lentiviral vector-based reporter assay to determine the HDR efficiencies in cella...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910002/the-rice-pentatricopeptide-repeat-gene-tcd10-is-needed-for-chloroplast-development-under-cold-stress
#5
Lanlan Wu, Jun Wu, Yanxia Liu, Xiaodi Gong, Jianlong Xu, Dongzhi Lin, Yanjun Dong
BACKGROUND: Chloroplast plays a vital role in plant development and growth. The pentatricopeptide repeat (PPR) gene family is one of the largest gene families in plants. In addition, cold stress affects a broad spectrum of cellular components, e.g. chloroplast, and metabolism in plants. However, the regulatory mechanism for rice PPR genes on chloroplast development still remains elusive under cold stress. RESULT: In this paper, we characterized a new rice PPR gene mutant tcd10 (thermo-sensitive chlorophyll-deficient mutant 10) that exhibits the albino phenotype, malformed chloroplast and could not survive after the 5-leaf stage when grown at 20 °C, but does the normal phenotype at 32 °C...
December 2016: Rice
https://www.readbyqxmd.com/read/27907896/harnessing-human-adar2-for-rna-repair-recoding-a-pink1-mutation-rescues-mitophagy
#6
Jacqueline Wettengel, Philipp Reautschnig, Sven Geisler, Philipp J Kahle, Thorsten Stafforst
Site-directed A-to-I RNA editing is a technology for re-programming genetic information at the RNA-level. We describe here the first design of genetically encodable guideRNAs that enable the re-addressing of human ADAR2 toward specific sites in user-defined mRNA targets. Up to 65% editing yield has been achieved in cell culture for the recoding of a premature Stop codon (UAG) into tryptophan (UIG). In the targeted gene, editing was very specific. We applied the technology to recode a recessive loss-of-function mutation in PINK1 (W437X) in HeLa cells and showed functional rescue of PINK1/Parkin-mediated mitophagy, which is linked to the etiology of Parkinson's disease...
October 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27905529/efficient-targeted-mutagenesis-of-rice-and-tobacco-genomes-using-cpf1-from-francisella-novicida
#7
Akira Endo, Mikami Masafumi, Hidetaka Kaya, Seiichi Toki
CRISPR/Cas9 systems are nowadays applied extensively to effect genome editing in various organisms including plants. CRISPR from Prevotella and Francisella 1 (Cpf1) is a newly characterized RNA-guided endonuclease that has two distinct features as compared to Cas9. First, Cpf1 utilizes a thymidine-rich protospacer adjacent motif (PAM) while Cas9 prefers a guanidine-rich PAM. Cpf1 could be used as a sequence-specific nuclease to target AT-rich regions of a genome that Cas9 had difficulty accessing. Second, Cpf1 generates DNA ends with a 5' overhang, whereas Cas9 creates blunt DNA ends after cleavage...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905063/efficient-gene-targeting-in-mouse-zygotes-mediated-by-crispr-cas9-protein
#8
Chris J Jung, Junli Zhang, Elizabeth Trenchard, Kent C Lloyd, David B West, Barry Rosen, Pieter J de Jong
The CRISPR/Cas9 system has rapidly advanced targeted genome editing technologies. However, its efficiency in targeting with constructs in mouse zygotes via homology directed repair (HDR) remains low. Here, we systematically explored optimal parameters for targeting constructs in mouse zygotes via HDR using mouse embryonic stem cells as a model system. We characterized several parameters, including single guide RNA cleavage activity and the length and symmetry of homology arms in the construct, and we compared the targeting efficiency between Cas9, Cas9nickase, and dCas9-FokI...
November 30, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27903241/abundant-rna-editing-sites-of-chloroplast-protein-coding-genes-in-ginkgo-biloba-and-an-evolutionary-pattern-analysis
#9
Peng He, Sheng Huang, Guanghui Xiao, Yuzhou Zhang, Jianing Yu
BACKGROUND: RNA editing is a posttranscriptional modification process that alters the RNA sequence so that it deviates from the genomic DNA sequence. RNA editing mainly occurs in chloroplasts and mitochondrial genomes, and the number of editing sites varies in terrestrial plants. Why and how RNA editing systems evolved remains a mystery. Ginkgo biloba is one of the oldest seed plants and has an important evolutionary position. Determining the patterns and distribution of RNA editing in the ancient plant provides insights into the evolutionary trend of RNA editing, and helping us to further understand their biological significance...
December 1, 2016: BMC Plant Biology
https://www.readbyqxmd.com/read/27900888/using-the-crispr-cas9-system-to-eliminate-native-plasmids-of-zymomonas-mobilis-zm4
#10
Qing-Hua Cao, Huan-Huan Shao, Hui Qiu, Tao Li, Yi-Zheng Zhang, Xue-Mei Tan
The CRISPR/Cas system can be used to simply and efficiently edit the genomes of various species, including animals, plants, and microbes. Zymomonas mobilis ZM4 is a highly efficient, ethanol-producing bacterium that contains five native plasmids. Here, we constructed the pSUZM2a-Cas9 plasmid and a single-guide RNA expression plasmid. The pSUZM2a-Cas9 plasmid was used to express the Cas9 gene cloned from Streptococcus pyogenes CICC 10464. The single-guide RNA expression plasmid pUC-T7sgRNA, with a T7 promoter, can be used for the in vitro synthesis of single-guide RNAs...
November 30, 2016: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27899663/large-scale-analysis-of-microrna-expression-epi-transcriptomic-features-and-biogenesis
#11
Dimitrios M Vitsios, Matthew P Davis, Stijn van Dongen, Anton J Enright
MicroRNAs are important genetic regulators in both animals and plants. They have a range of functions spanning development, differentiation, growth, metabolism and disease. The advent of next-generation sequencing technologies has made it a relatively straightforward task to detect these molecules and their relative expression via sequencing. There are a large number of published studies with deposited datasets. However, there are currently few resources that capitalize on these data to better understand the features, distribution and biogenesis of miRNAs...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27896396/metabolic-profiling-of-ob-ob-mouse-fatty-liver-using-hr-mas-1-h-nmr-combined-with-gene-expression-analysis-reveals-alterations-in-betaine-metabolism-and-the-transsulfuration-pathway
#12
Mikheil Gogiashvili, Karolina Edlund, Kathrin Gianmoena, Rosemarie Marchan, Alexander Brik, Jan T Andersson, Jörg Lambert, Katrin Madjar, Birte Hellwig, Jörg Rahnenführer, Jan G Hengstler, Roland Hergenröder, Cristina Cadenas
Metabolic perturbations resulting from excessive hepatic fat accumulation are poorly understood. Thus, in this study, leptin-deficient ob/ob mice, a mouse model of fatty liver disease, were used to investigate metabolic alterations in more detail. Metabolites were quantified in intact liver tissues of ob/ob (n = 8) and control (n = 8) mice using high-resolution magic angle spinning (HR-MAS) (1)H-NMR. In addition, after demonstrating that HR-MAS (1)H-NMR does not affect RNA integrity, transcriptional changes were measured by quantitative real-time PCR on RNA extracted from the same specimens after HR-MAS (1)H-NMR measurements...
November 28, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27893733/adarb1-catalyzes-circadian-a-to-i-editing-and-regulates-rna-rhythm
#13
Hideki Terajima, Hikari Yoshitane, Haruka Ozaki, Yutaka Suzuki, Shigeki Shimba, Shinya Kuroda, Wataru Iwasaki, Yoshitaka Fukada
It has been proposed that the CLOCK-ARNTL (BMAL1) complex drives circadian transcription of thousands of genes, including Per and Cry family genes that encode suppressors of CLOCK-ARNTL-dependent transcription. However, recent studies demonstrated that 70-80% of circadian-oscillating mRNAs have no obvious rhythms in their de novo transcription, indicating the potential importance of post-transcriptional regulation. Our CLOCK-ChIP-seq analysis identified rhythmic expression of adenosine deaminase, RNA-specific, B1 (Adarb1, also known as Adar2), an adenosine-to-inosine (A-to-I) RNA-editing enzyme...
November 28, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27891578/dual-specificity-phosphatase-15-regulates-erk-activation-in-schwann-cells
#14
José F Rodríguez-Molina, Camila Lopez-Anido, Ki H Ma, Chongyu Zhang, Tyler Olson, Katharina N Muth, Matthias Weider, John Svaren
Schwann cells and oligodendrocytes are the myelinating cells of the peripheral and central nervous system, respectively. Despite having different myelin components and different transcription factors driving their terminal differentiation there are shared molecular mechanisms between the two. Sox10 is one common transcription factor required for several steps in development of myelinating glia. However, other factors are divergent as Schwann cells need the transcription factor Egr2/Krox20 and oligodendrocytes require Myrf...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27890617/polycistronic-trna-and-crispr-guide-rna-enables-highly-efficient-multiplexed-genome-engineering-in-human-cells
#15
Fengping Dong, Kabin Xie, Yueying Chen, Yinong Yang, Yingwei Mao
CRISPR/Cas9 has been widely used for genomic editing in many organisms. Many human diseases are caused by multiple mutations. The CRISPR/Cas9 system provides a potential tool to introduce multiple mutations in a genome. To mimic complicated genomic events in human diseases, such as multiple gene deletions or mutations, two or more small guide RNAs (sgRNA) must be introduced all together. This can be achieved by separate Pol III promoters in a construct. However, limited enzyme sites and the increased insertion size lower the efficiency to make a construct...
November 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27884627/characterization-of-avian-paramyxovirus-serotype-14-a-novel-serotype-isolated-from-a-duck-fecal-sample-in-japan
#16
Rapeewan Thampaisarn, Vuong N Bui, Dai Q Trinh, Makoto Nagai, Tetsuya Mizutani, Tsutomu Omatsu, Yukie Katayama, Dulyatad Gronsang, Duong H T Le, Haruko Ogawa, Kunitoshi Imai
A hemagglutinating virus isolate designated 11OG0352, was obtained from a duck fecal sample. Genetic and virological analyses indicated that it might represent a novel serotype of avian paramyxovirus (APMV). Electron micrographs showed that the morphology of the virus particle was similar to that of APMV. The complete genome of this virus comprised 15,444 nucleotides complying with the paramyxovirus "rule of six" and contains six open reading frames (3'-N-P-M-F-HN-L-5'). The phylogenetic analysis of the whole genome revealed that the virus was a member of the genus Avulavirus, but that it was distinct from APMV-1 to APMV-13...
November 21, 2016: Virus Research
https://www.readbyqxmd.com/read/27878142/microrna-biogenesis-epigenetic-modifications-as-another-layer-of-complexity-in-the-microrna-expression-regulation
#17
Susheel Sagar Bhat, Artur Jarmolowski, Zofia Szweykowska-Kulińska
Since their discovery, microRNAs have led to a huge shift in our understanding of the regulation of key biological processes. The discovery of epigenetic modifications that affect microRNA expression has added another layer of complexity to the already tightly controlled regulatory machinery. Modifications like uridylation, adenylation and RNA editing have been shown to have variable effects on miRNA biogenesis and action. Methylation of the N6 adenosine has been studied extensively in mRNA. Presence of the N6-methyl-adenosine (m(6)A) mark and its critical importance in miRNA biogenesis in animals adds to our understanding of the regulatory mechanisms, while its effect on miRNA biogenesis in plants is yet to be understood...
November 22, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27874090/a-novel-process-of-viral-vector-barcoding-and-library-preparation-enables-high-diversity-library-generation-and-recombination-free-paired-end-sequencing
#18
Marcus Davidsson, Paula Diaz-Fernandez, Oliver D Schwich, Marcos Torroba, Gang Wang, Tomas Björklund
Detailed characterization and mapping of oligonucleotide function in vivo is generally a very time consuming effort that only allows for hypothesis driven subsampling of the full sequence to be analysed. Recent advances in deep sequencing together with highly efficient parallel oligonucleotide synthesis and cloning techniques have, however, opened up for entirely new ways to map genetic function in vivo. Here we present a novel, optimized protocol for the generation of universally applicable, barcode labelled, plasmid libraries...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27874072/cas9-catalyzed-dna-cleavage-generates-staggered-ends-evidence-from-molecular-dynamics-simulations
#19
Zhicheng Zuo, Jin Liu
The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (spCas9) along with a single guide RNA (sgRNA) has emerged as a versatile toolbox for genome editing. Despite recent advances in the mechanism studies on spCas9-sgRNA-mediated double-stranded DNA (dsDNA) recognition and cleavage, it is still unclear how the catalytic Mg(2+) ions induce the conformation changes toward the catalytic active state. It also remains controversial whether Cas9 generates blunt-ended or staggered-ended breaks with overhangs in the DNA...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27870265/antizyme-inhibitor-1-a-potential-carcinogenic-molecule
#20
REVIEW
Shiqiao Qiu, Jing Liu, Feiyue Xing
Polyamines are multivalent and organic cations essential for cellular growth, proliferation, differentiation and apoptosis. Increased levels of polyamines are closely associated with numerous forms of cancer. An autoregulatory circuit composed by the ornithine decarboxylase(ODC), antizymes(AZ) and antizyme inhibitor (AZI) governs the intracellular level of polyamines. AZ binds with ODC to inhibit the ODC activity and to promote the ubiquitin-independent degradation of ODC. AZI binds to AZ with a higher affinity than ODC...
November 21, 2016: Cancer Science
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