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Nucleic Acids Research

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https://www.readbyqxmd.com/read/29452381/a-fungal-argonaute-interferes-with-rna-interference
#1
Quyet Nguyen, Akihide Iritani, Shuhei Ohkita, Ba V Vu, Kana Yokoya, Ai Matsubara, Ken-Ichi Ikeda, Nobuhiro Suzuki, Hitoshi Nakayashiki
No abstract text is available yet for this article.
February 14, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29447396/rna-dna-hybrids-promote-the-expansion-of-friedreich-s-ataxia-gaa-n-repeats-via-break-induced-replication
#2
Alexander J Neil, Miranda U Liang, Alexandra N Khristich, Kartik A Shah, Sergei M Mirkin
Expansion of simple DNA repeats is responsible for numerous hereditary diseases in humans. The role of DNA replication, repair and transcription in the expansion process has been well documented. Here we analyzed, in a yeast experimental system, the role of RNA-DNA hybrids in genetic instability of long (GAA)n repeats, which cause Friedreich's ataxia. Knocking out both yeast RNase H enzymes, which counteract the formation of RNA-DNA hybrids, increased (GAA)n repeat expansion and contraction rates when the repetitive sequence was transcribed...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29447394/human-la-binds-mrnas-through-contacts-to-the-poly-a-tail
#3
Jyotsna Vinayak, Stefano A Marrella, Rawaa H Hussain, Leonid Rozenfeld, Karine Solomon, Mark A Bayfield
In addition to a role in the processing of nascent RNA polymerase III transcripts, La proteins are also associated with promoting cap-independent translation from the internal ribosome entry sites of numerous cellular and viral coding RNAs. La binding to RNA polymerase III transcripts via their common UUU-3'OH motif is well characterized, but the mechanism of La binding to coding RNAs is poorly understood. Using electromobility shift assays and cross-linking immunoprecipitation, we show that in addition to a sequence specific UUU-3'OH binding mode, human La exhibits a sequence specific and length dependent poly(A) binding mode...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29447390/pold3-is-required-for-genomic-stability-and-telomere-integrity-in-embryonic-stem-cells-and-meiosis
#4
Zhongcheng Zhou, Lingling Wang, Feixiang Ge, Peng Gong, Hua Wang, Feng Wang, Lingyi Chen, Lin Liu
Embryonic stem cells (ESCs) and meiosis are featured by relatively higher frequent homologous recombination associated with DNA double strand breaks (DSB) repair. Here, we show that Pold3 plays important roles in DSB repair, telomere maintenance and genomic stability of both ESCs and spermatocytes in mice. By attempting to generate Pold3 deficient mice using CRISPR/Cas9 or transcription activator-like effector nucleases, we show that complete loss of Pold3 (Pold3-/-) resulted in early embryonic lethality at E6...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29447387/ezh2-promotes-clock-function-and-hematopoiesis-independent-of-histone-methyltransferase-activity-in-zebrafish
#5
Yingbin Zhong, Qiang Ye, Chengyan Chen, Mingyong Wang, Han Wang
EZH2 is a subunit of polycomb repressive complex 2 (PRC2) that silences gene transcription via H3K27me3 and was shown to be essential for mammalian liver circadian regulation and hematopoiesis through gene silencing. Much less, however, is known about how Ezh2 acts in live zebrafish. Here, we show that zebrafish ezh2 is regulated directly by the circadian clock via both E-box and RORE motif, while core circadian clock genes per1a, per1b, cry1aa and cry1ab are down-regulated in ezh2 null mutant and ezh2 morphant zebrafish, and either knockdown or overexpression of ezh2 alters locomotor rhythms, indicating that Ezh2 is required for zebrafish circadian regulation...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29447383/super-resolution-imaging-identifies-parp1-and-the-ku-complex-acting-as-dna-double-strand-break-sensors
#6
Guang Yang, Chao Liu, Shih-Hsun Chen, Muzaffer A Kassab, J Damon Hoff, Nils G Walter, Xiaochun Yu
DNA double-strand breaks (DSBs) are fatal DNA lesions and activate a rapid DNA damage response. However, the earliest stage of DSB sensing remains elusive. Here, we report that PARP1 and the Ku70/80 complex localize to DNA lesions considerably earlier than other DSB sensors. Using super-resolved fluorescent particle tracking, we further examine the relocation kinetics of PARP1 and the Ku70/80 complex to a single DSB, and find that PARP1 and the Ku70/80 complex are recruited to the DSB almost at the same time...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29447381/dna-mismatch-repair-and-oligonucleotide-end-protection-promote-base-pair-substitution-distal-from-a-crispr-cas9-induced-dna-break
#7
Tim Harmsen, Sjoerd Klaasen, Henri van de Vrugt, Hein Te Riele
Single-stranded oligodeoxyribonucleotide (ssODN)-mediated repair of CRISPR/Cas9-induced DNA double-strand breaks (DSB) can effectively be used to introduce small genomic alterations in a defined locus. Here, we reveal DNA mismatch repair (MMR) activity is crucial for efficient nucleotide substitution distal from the Cas9-induced DNA break when the substitution is instructed by the 3' half of the ssODN. Furthermore, protecting the ssODN 3' end with phosphorothioate linkages enhances MMR-dependent gene editing events...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29447373/coupling-the-core-of-the-anticancer-drug-etoposide-to-an-oligonucleotide-induces-topoisomerase-ii-mediated-cleavage-at-specific-dna-sequences
#8
Lorena Infante Lara, Sabine Fenner, Steven Ratcliffe, Albert Isidro-Llobet, Michael Hann, Ben Bax, Neil Osheroff
Etoposide and other topoisomerase II-targeted drugs are important anticancer therapeutics. Unfortunately, the safe usage of these agents is limited by their indiscriminate induction of topoisomerase II-mediated DNA cleavage throughout the genome and by a lack of specificity toward cancer cells. Therefore, as a first step toward constraining the distribution of etoposide-induced DNA cleavage sites and developing sequence-specific topoisomerase II-targeted anticancer agents, we covalently coupled the core of etoposide to oligonucleotides centered on a topoisomerase II cleavage site in the PML gene...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29438559/oxidative-stress-increases-m1dg-a-major-peroxidation-derived-dna-adduct-in-mitochondrial-dna
#9
Orrette R Wauchope, Michelle M Mitchener, William N Beavers, James J Galligan, Jeannie M Camarillo, William D Sanders, Philip J Kingsley, Ha-Na Shim, Thomas Blackwell, Thong Luong, Mark deCaestecker, Joshua P Fessel, Lawrence J Marnett
Reactive oxygen species (ROS) are formed in mitochondria during electron transport and energy generation. Elevated levels of ROS lead to increased amounts of mitochondrial DNA (mtDNA) damage. We report that levels of M1dG, a major endogenous peroxidation-derived DNA adduct, are 50-100-fold higher in mtDNA than in nuclear DNA in several different human cell lines. Treatment of cells with agents that either increase or decrease mitochondrial superoxide levels leads to increased or decreased levels of M1dG in mtDNA, respectively...
February 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29438503/lineage-specific-transcription-factors-and-epigenetic-regulators-mediate-tgf%C3%AE-dependent-enhancer-activation
#10
Raquel Fueyo, Simona Iacobucci, Stella Pappa, Conchi Estarás, Sergio Lois, Marta Vicioso-Mantis, Claudia Navarro, Sara Cruz-Molina, José Carlos Reyes, Álvaro Rada-Iglesias, Xavier de la Cruz, Marian A Martínez-Balbás
During neurogenesis, dynamic developmental cues, transcription factors and histone modifying enzymes regulate the gene expression programs by modulating the activity of neural-specific enhancers. How transient developmental signals coordinate transcription factor recruitment to enhancers and to which extent chromatin modifiers contribute to enhancer activity is starting to be uncovered. Here, we take advantage of neural stem cells as a model to unravel the mechanisms underlying neural enhancer activation in response to the TGFβ signaling...
February 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29438499/ksp1-dependent-phosphorylation-of-eif4g-modulates-post-transcriptional-regulation-of-specific-mrnas-under-glucose-deprivation-conditions
#11
Yeonji Chang, Won-Ki Huh
Post-transcriptional regulation is an important mechanism for modulating gene expression and is performed by numerous mRNA-binding proteins. To understand the mechanisms underlying post-transcriptional regulation, we investigated the phosphorylation status of 32 mRNA-binding proteins under glucose deprivation conditions in Saccharomyces cerevisiae. We identified 17 glucose-sensitive phosphoproteins and signal pathways implicated in their phosphorylation. Notably, phosphorylation of the eukaryotic translation initiation factor 4G (eIF4G) was regulated by both the Snf1/AMPK pathway and the target of rapamycin complex 1 (TORC1) pathway...
February 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29432616/autoregulation-of-mazef-expression-underlies-growth-heterogeneity-in-bacterial-populations
#12
Nela Nikolic, Tobias Bergmiller, Alexandra Vandervelde, Tanino G Albanese, Lendert Gelens, Isabella Moll
The MazF toxin sequence-specifically cleaves single-stranded RNA upon various stressful conditions, and it is activated as a part of the mazEF toxin-antitoxin module in Escherichia coli. Although autoregulation of mazEF expression through the MazE antitoxin-dependent transcriptional repression has been biochemically characterized, less is known about post-transcriptional autoregulation, as well as how both of these autoregulatory features affect growth of single cells during conditions that promote MazF production...
February 8, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29432594/nuclear-import-of-cdc13-limits-chromosomal-capping
#13
Sofiane Y Mersaoui, Erin Bonnell, Raymund J Wellinger
Cdc13 is an essential protein involved in telomere maintenance and chromosome capping. Individual domain analyses on Cdc13 suggest the presence of four distinct OB-fold domains and one recruitment domain. However, it remained unclear how these sub-domains function in the context of the whole protein in vivo. Here, we use individual single domain deletions to address their roles in telomere capping. We find that the OB2 domain contains a nuclear localization signal that is essential for nuclear import of Cdc13 and therefore is required for chromosome capping...
February 8, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29432582/structural-rearrangements-in-the-mitochondrial-genome-of-drosophila-melanogaster-induced-by-elevated-levels-of-the-replicative-dna-helicase
#14
Grzegorz L Ciesielski, Cristina A Nadalutti, Marcos T Oliveira, Howard T Jacobs, Jack D Griffith, Laurie S Kaguni
Pathological conditions impairing functions of mitochondria often lead to compensatory upregulation of the mitochondrial DNA (mtDNA) replisome machinery, and the replicative DNA helicase appears to be a key factor in regulating mtDNA copy number. Moreover, mtDNA helicase mutations have been associated with structural rearrangements of the mitochondrial genome. To evaluate the effects of elevated levels of the mtDNA helicase on the integrity and replication of the mitochondrial genome, we overexpressed the helicase in Drosophila melanogaster Schneider cells and analyzed the mtDNA by two-dimensional neutral agarose gel electrophoresis and electron microscopy...
February 8, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29432573/selection-periodicity-and-potential-function-for-highly-iterative-palindrome-1-hip1-in-cyanobacterial-genomes
#15
Minli Xu, Jeffrey G Lawrence, Dannie Durand
Highly Iterated Palindrome 1 (HIP1, GCGATCGC) is hyper-abundant in most cyanobacterial genomes. In some cyanobacteria, average HIP1 abundance exceeds one motif per gene. Such high abundance suggests a significant role in cyanobacterial biology. However, 20 years of study have not revealed whether HIP1 has a function, much less what that function might be. We show that HIP1 is 15- to 300-fold over-represented in genomes analyzed. More importantly, HIP1 sites are conserved both within and between open reading frames, suggesting that their overabundance is maintained by selection rather than by continual replenishment by neutral processes, such as biased DNA repair...
February 8, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29432571/comparison-of-partially-and-fully-chemically-modified-sirna-in-conjugate-mediated-delivery-in-vivo
#16
Matthew R Hassler, Anton A Turanov, Julia F Alterman, Reka A Haraszti, Andrew H Coles, Maire F Osborn, Dimas Echeverria, Mehran Nikan, William E Salomon, Loïc Roux, Bruno M D C Godinho, Sarah M Davis, David V Morrissey, Phillip D Zamore, S Ananth Karumanchi, Melissa J Moore, Neil Aronin, Anastasia Khvorova
Small interfering RNA (siRNA)-based drugs require chemical modifications or formulation to promote stability, minimize innate immunity, and enable delivery to target tissues. Partially modified siRNAs (up to 70% of the nucleotides) provide significant stabilization in vitro and are commercially available; thus are commonly used to evaluate efficacy of bio-conjugates for in vivo delivery. In contrast, most clinically-advanced non-formulated compounds, using conjugation as a delivery strategy, are fully chemically modified (100% of nucleotides)...
February 8, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29432565/an-rna-dependent-mechanism-for-transient-expression-of-bacterial-translocation-filaments
#17
Dai Wang, Sean P McAteer, Agata B Wawszczyk, Clark D Russell, Amin Tahoun, Alex Elmi, Scott L Cockroft, David Tollervey, Sander Granneman, Jai J Tree, David L Gally
The prokaryotic RNA chaperone Hfq mediates sRNA-mRNA interactions and plays a significant role in post-transcriptional regulation of the type III secretion (T3S) system produced by a range of Escherichia coli pathotypes. UV-crosslinking was used to map Hfq-binding under conditions that promote T3S and multiple interactions were identified within polycistronic transcripts produced from the locus of enterocyte effacement (LEE) that encodes the T3S system. The majority of Hfq binding was within the LEE5 and LEE4 operons, the latter encoding the translocon apparatus (SepL-EspADB) that is positively regulated by the RNA binding protein, CsrA...
February 8, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29425356/uniprot-the-universal-protein-knowledgebase
#18
(no author information available yet)
No abstract text is available yet for this article.
February 7, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29425321/splicing-regulation-by-long-noncoding-rnas
#19
Natali Romero-Barrios, Maria Florencia Legascue, Moussa Benhamed, Federico Ariel, Martin Crespi
Massive high-throughput sequencing techniques allowed the identification of thousands of noncoding RNAs (ncRNAs) and a plethora of different mRNA processing events occurring in higher organisms. Long ncRNAs can act directly as long transcripts or can be processed into active small si/miRNAs. They can modulate mRNA cleavage, translational repression or the epigenetic landscape of their target genes. Recently, certain long ncRNAs have been shown to play a crucial role in the regulation of alternative splicing in response to several stimuli or during disease...
February 7, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29425303/regulation-of-the-positive-transcriptional-effect-of-plzf-through-a-non-canonical-ezh2-activity
#20
Myriam Koubi, Mathilde Poplineau, Julien Vernerey, Lia N'Guyen, Guillaume Tiberi, Sylvain Garciaz, Abdessamad El-Kaoutari, Muhammad A Maqbool, Jean-Christophe Andrau, Christel Guillouf, Andrew J Saurin, Estelle Duprez
The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes. Additionally, we identify a new association between PLZF and the histone methyltransferase, EZH2 at the genomic level...
February 7, 2018: Nucleic Acids Research
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