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https://www.readbyqxmd.com/read/28432356/a-role-of-human-rnase-p-subunits-rpp29-and-rpp21-in-homology-directed-repair-of-double-strand-breaks
#1
Enas R Abu-Zhayia, Hanan Khoury-Haddad, Noga Guttmann-Raviv, Raphael Serruya, Nayef Jarrous, Nabieh Ayoub
DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to advance the understanding of the molecular mechanisms by which cells keep their genetic material intact. Here, we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431232/genome-wide-mapping-of-drosha-cleavage-sites-on-primary-micrornas-and-noncanonical-substrates
#2
Baekgyu Kim, Kyowon Jeong, V Narry Kim
MicroRNA (miRNA) maturation is initiated by DROSHA, a double-stranded RNA (dsRNA)-specific RNase III enzyme. By cleaving primary miRNAs (pri-miRNAs) at specific positions, DROSHA serves as a main determinant of miRNA sequences and a highly selective gatekeeper for the canonical miRNA pathway. However, the sites of DROSHA-mediated processing have not been annotated, and it remains unclear to what extent DROSHA functions outside the miRNA pathway. Here, we establish a protocol termed "formaldehyde crosslinking, immunoprecipitation, and sequencing (fCLIP-seq)," which allows identification of DROSHA cleavage sites at single-nucleotide resolution...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28423658/correlation-between-polymorphisms-in-microrna-regulated-genes-and-cervical-cancer-susceptibility-in-a-xinjiang-uygur-population
#3
Jing Fang, Ying Li, Jiayi Zhang, Mengdan Yan, Jingjie Li, Shan Bao, Tianbo Jin
We explored the correlation between single nucleotide polymorphisms (SNPs) and susceptibility to cervical cancer (CC) in a Xinjiang Uygur population. Ten SNPs in eight miRNA-regulated genes were selected for analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to detect correlations between SNPs and CC. We found that minor allele "C" of rs512715 in NEAT1 was associated with an increased risk of CC in the allele, codominant, dominant, overdominant and log-additive models...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421985/design-of-a-sensitive-and-selective-electrochemical-aptasensor-for-the-determination-of-the-complementary-cdna-of-mirna-145-based-on-the-intercalation-and-electrochemical-reduction-of-doxorubicin
#4
Maryam Mohamadi, Ali Mostafavi, Masoud Torkzadeh-Mahani
<p>The aim of this research was the determination of a microRNA (miRNA) using a DNA electrochemical aptasensor. In this biosensor, the complementary complementary DNA (cDNA) of miRNA-145 (a sense RNA transcript) was the target strand and the cDNA of miRNA-145 was the probe strand. Both cDNAs can be the product of the reverse transcriptase-polymerase chain reaction of miRNA. The proposed aptasensor's function was based on the hybridization of target strands with probes immobilized on the surface of a working electrode and the subsequent intercalation of doxorubicin (DOX) molecules functioning as the electroactive indicators of any double strands that formed...
April 19, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28418037/mitochondrial-c11orf83-is-a-potent-antiviral-protein-independent-of-interferon-production
#5
Yun Yang, Shaoquan Xiong, Bei Cai, Hui Luo, E Dong, Qiqi Li, Gaili Ji, Chengjian Zhao, Yanjun Wen, Yuquan Wei, Hanshuo Yang
Mitochondria have a central position in innate immune response via the adaptor protein MAVS in mitochondrial outer membrane to limit viral replication by inducing interferon production. Here, we reported that C11orf83, a component of complex III of electronic transfer chain in mitochondrial inner membrane, was a potent antiviral protein independent of interferon production. C11orf83 expression significantly increased in response to viral infection, and endows cells with stronger capability of inhibiting viral replication...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416706/the-gan-exonuclease-or-the-flap-endonuclease-fen1-and-rnase-hii-are-necessary-for-viability-of-thermococcus-kodakarensis
#6
Brett W Burkhart, Lubomira Cubonova, Margaret R Heider, Zvi Kelman, John N Reeve, Thomas J Santangelo
Many aspects of and factors required for DNA replication are conserved across all three Domains of life but there are some significant differences surrounding lagging strand synthesis. In Archaea, a 5' to 3' exonuclease, related to both bacterial RecJ and eukaryotic Cdc45, that associates with the replisome specifically through interactions with GINS, was identified and designated GAN (for GINS-associated nuclease). Despite the presence of a well-characterized flap endonuclease (Fen1), it was hypothesized that GAN might participate in primer removal during Okazaki fragment maturation and, as a Cdc45 homologue, GAN might also be a structural component of an archaeal CMG (Cdc45, MCM, GINS) replication complex...
April 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28412325/designing-metal-contained-enzyme-mimics-for-prodrug-activation
#7
REVIEW
Baoji Du, Dan Li, Jin Wang, Erkang Wang
Enzyme-activated prodrug therapy (EAPT) is a widely-used and effective treatment method for cancer by converting the prodrugs into the drugs at the demanded time and space, whose key step is prodrug activation. Traditional prodrug activations are mostly dependent on the natural enzymes, which are unstable, expensive and hard to be functionalized. The emerging enzyme mimics, especially the metal-contained enzyme mimics (MEMs), provide a potential chance for improving the traditional EAPT because of their high stability, low cost and easiness of preparation and functionalization...
April 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28410117/racial-disparities-disruptive-genes-in-prostate-carcinogenesis
#8
Savita Singh, Alexis Plaga, Girish C Shukla
Population specific studies in prostate cancer (PCa) reveal a unique heterogeneous etiology. Various factors, such as genetics, environment and dietary regimen seems to determine disease progression, therapeutic resistance and rate of mortality. Enormous disparity documented in disease incidences, aggressiveness and mortality in PCa among AAs (African Americans) and CAs (Caucasian Americans) is attributed to the variations in genetics, epigenetics and their association with metabolism. Scientific and clinical evidences have revealed the influence of variations in Androgen Receptor (AR), RNAse L, macrophage scavenger receptor 1 (MRS1), androgen metabolism by cytochrome P450 3A4, differential regulation of microRNAs, epigenetic alterations and diet in racial disparity in PCa incidences and mortality...
June 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28408723/nucleic-acid-detection-with-crispr-cas13a-c2c2
#9
Jonathan S Gootenberg, Omar O Abudayyeh, Jeong Wook Lee, Patrick Essletzbichler, Aaron J Dy, Julia Joung, Vanessa Verdine, Nina Donghia, Nichole M Daringer, Catherine A Freije, Cameron Myhrvold, Roby P Bhattacharyya, Jonathan Livny, Aviv Regev, Eugene V Koonin, Deborah T Hung, Pardis C Sabeti, James J Collins, Feng Zhang
Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting CRISPR effector Cas13a (previously known as C2c2) exhibits a "collateral effect" of promiscuous RNAse activity upon target recognition. We combine the collateral effect of Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity...
April 13, 2017: Science
https://www.readbyqxmd.com/read/28408394/a-close-up-look-at-the-spliceosome-at-last
#10
John Abelson
Major developments in cryo-electron microscopy in the past three or four years have led to the solution of a number of spliceosome structures at high resolution, e.g., the fully assembled but not yet active spliceosome (Bact), the spliceosome just after the first step of splicing (C), and the spliceosome activated for the second step (C*). Therefore 30 years of genetics and biochemistry of the spliceosome can now be interpreted at the structural level. I have closely examined the RNase H domain of Prp8 in each of the structures...
April 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28406067/rna-and-a-cell-wall-component-of-enterococcus-faecalis-ic-1-are-required-for-phagocytosis-and-interleukin-12-production-by-the-mouse-macrophage-cell-line-j774-1
#11
Junpei Nakase, Yuuichi Ukawa, Syoji Takemoto, Takayoshi Kubo, Yuko M Sagesaka, Ayako Aoki-Yoshida, Mamoru Totsuka
Enterococcus faecalis is a resident lactic acid bacterium in the human intestine. Its immunostimulatory action was reported to be enhanced by heat sterilization. To investigate its beneficial actions, we evaluated the ability of 10 E. faecalis strains to induce interleukin-12 (IL-12) production in a mouse macrophage cell line, J774.1 and found that the strain, E. faecalis IC-1, had a potent IL-12-inducing ability. Furthermore, we investigated the underlying mechanism by treating IC-1 cells with RNase or lysozyme...
April 13, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28404679/evaluation-of-taqman-array-card-tac-for-the-detection-of-central-nervous-system-infections-in-kenya
#12
Clayton O Onyango, Vladimir Loparev, Shirley Lidechi, Vinod Bhullar, D Scott Schmid, Kay Radford, Michael K Lo, Paul Rota, Barbara W Johnson, Jorge Munoz, Martina Oneko, Deron Burton, Carolyn M Black, John Neatherlin, Joel M Montgomery, Barry Fields
Infections of the central nervous system (CNS) are often acute with significant morbidity and mortality. Routine diagnosis of such infections is limited in developing countries and requires modern equipment in advanced laboratories that may be unavailable to a number of patients in sub-Saharan Africa. We developed a TaqMan Array Card (TAC) that detects multiple pathogens simultaneously from cerebrospinal fluid (CSF). The 21-pathogen TAC assays include two parasites (Balamuthia mandrillaris and Acanthamoeba), six bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Mycoplasma pneumoniae, Mycobacterium tuberculosis, and Bartonella) and 13 viruses (parechovirus, dengue, nipah, varicella zoster, mumps, measles, lyssa, herpes simplex virus 1 and 2, Epstein Barr virus, enterovirus, cytomegalovirus and chikungunya)...
April 12, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28402412/effects-of-neutral-salts-and-ph-on-the-activity-and-stability-of-human-rnase-h2
#13
Misato Baba, Kenji Kojima, Rihoko Nakase, Shota Imai, Tomomi Yamasaki, Teisuke Takita, Robert J Crouch, Kiyoshi Yasukawa
Ribonuclease H (RNase H) specifically degrades the RNA of RNA/DNA hybrid. Recent study has shown that a single ribonucleotide is embedded in DNA double strand at every few thousand base pairs in human genome, and human RNase H2 is involved in its removal. Here, we examined the effects of neutral salts and pH on the activity and stability of human RNase H2. NaCl, KCl, RbCl, and NaBr increased the activity to 170-390% at 10-60 mM, while LiCl, LiBr, and CsCl inhibited it, suggesting that species of cation, but not anion, is responsible for the effect on activity...
April 11, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28400719/reduction-of-huntington-s-disease-rna-foci-by-cag-repeat-targeting-reagents
#14
Martyna O Urbanek, Agnieszka Fiszer, Wlodzimierz J Krzyzosiak
In several human polyglutamine diseases caused by expansions of CAG repeats in the coding sequence of single genes, mutant transcripts are detained in nuclear RNA foci. In polyglutamine disorders, unlike other repeat-associated diseases, both RNA and proteins exert pathogenic effects; therefore, decreases of both RNA and protein toxicity need to be addressed in proposed treatments. A variety of oligonucleotide-based therapeutic approaches have been developed for polyglutamine diseases, but concomitant assays for RNA foci reduction are lacking...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28400409/drosha-targets-its-own-transcript-to-modulate-alternative-splicing
#15
Dooyoung Lee, Jin-Wu Nam, Chanseok Shin
The nuclear RNase III enzyme DROSHA interacts with its cofactor DGCR8 to form the Microprocessor complex, which initiates microRNA (miRNA) maturation by cleaving hairpin structures embedded in primary transcripts. Apart from its central role in the biogenesis of miRNAs, DROSHA is also known to recognize and cleave miRNA-like hairpins in a subset of transcripts without apparent small RNA production. Here, we report that the human DROSHA transcript is one such non-canonical target of DROSHA. Mammalian DROSHA genes have evolved a conserved hairpin structure spanning a specific exon-intron junction, which serves as a substrate for the Microprocessor in human cells but not in murine cells...
April 11, 2017: RNA
https://www.readbyqxmd.com/read/28399925/human-serum-rnase-l-level-is-inversely-associated-with-metabolic-syndrome-and-age
#16
Yi-Ting Wang, Ping-Huei Tseng, Chi-Ling Chen, Der-Sheng Han, Yu-Chiao Chi, Fen-Yu Tseng, Wei-Shiung Yang
BACKGROUND: Ribonuclease-L (RNase-L) was known to be a ubiquitous enzyme involved in several cellular functions, especially innate immunity. It was recently shown to participate in adipogenesis in rodents. Here, we developed a method to measure serum levels of RNase-L and analyzed the relationship between RNase-L and metabolic syndrome (MetS). METHODS: A total of 396 subjects were recruited from a health check-up program. An in-house RNase-L immunoassay was developed...
April 11, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28398546/the-cdi-toxin-ofyersinia-kristensenii-is-a-novel-bacterial-member-of-the-rnase-a-superfamily
#17
Gaëlle Batot, Karolina Michalska, Greg Ekberg, Ervin M Irimpan, Grazyna Joachimiak, Robert Jedrzejczak, Gyorgy Babnigg, Christopher S Hayes, Andrzej Joachimiak, Celia W Goulding
Contact-dependent growth inhibition (CDI) is an important mechanism of inter-bacterial competition found in many Gram-negative pathogens. CDI+ cells express cell-surface CdiA proteins that bind neighboring bacteria and deliver C-terminal toxin domains (CdiA-CT) to inhibit target-cell growth. CDI+ bacteria also produce CdiI immunity proteins, which specifically neutralize cognate CdiA-CT toxins to prevent self-inhibition. Here, we present the crystal structure of the CdiA-CT/CdiIYkris complex from Yersinia kristensenii ATCC 33638...
April 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28396352/association-of-the-cold-shock-dead-box-rna-helicase-rhle-to-the-rna-degradosome-in-caulobacter-crescentus
#18
Angel A Aguirre, Alexandre M Vicente, Steven W Hardwick, Daniela M Alvelos, Ricardo R Mazzon, Ben F Luisi, Marilis V Marques
In diverse bacterial lineages, multi-enzyme assemblies have evolved that are central elements of RNA metabolism and RNA-mediated regulation. The aquatic, Gram-negative bacteria Caulobacter crescentus, which has been a model system for studying the bacterial cell cycle, has an RNA degradosome assembly that is formed by the endoribonuclease RNase E and includes the DEAD-box RNA helicase RhlB. Immunoprecipitations of extracts from cells expressing an epitope-tagged RNase E reveal that RhlE, another member of the DEAD-box helicase family, associates with the degradosome at temperatures below the optimum for growth...
April 10, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28384548/synthesis-biological-evaluation-and-molecular-modeling-of-2-hydroxyisoquinoline-1-3-dione-analogues-as-inhibitors-of-hiv-reverse-transcriptase-associated-ribonuclease-h-and-polymerase
#19
Jing Tang, Sanjeev Kumar V Vernekar, Yue-Lei Chen, Lena Miller, Andrew D Huber, Nataliya Myshakina, Stefan G Sarafianos, Michael A Parniak, Zhengqiang Wang
Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function not clinically validated as an antiviral target. 2-Hydroxyisoquinoline-1,3-dione (HID) is known to confer active site directed inhibition of divalent metal-dependent enzymatic functions, such as HIV RNase H, integrase (IN) and hepatitis C virus (HCV) NS5B polymerase. We report herein the synthesis and biochemical evaluation of a few C-5, C-6 or C-7 substituted HID subtypes as HIV RNase H inhibitors...
March 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28384222/functional-studies-of-e-faecalis-rnase-j2-and-its-role-in-virulence-and-fitness
#20
Peng Gao, Kenneth L Pinkston, Agathe Bourgogne, Barbara E Murray, Ambro van Hoof, Barrett R Harvey
Post-transcriptional control provides bacterial pathogens a method by which they can rapidly adapt to environmental change. Dual exo- and endonucleolytic activities of RNase J enzymes contribute to Gram-positive RNA processing and decay. First discovered in Bacillus subtilis, RNase J1 plays a key role in mRNA maturation and degradation, while the function of the paralogue RNase J2 is largely unknown. Previously, we discovered that deletion of the Enterococcus faecalis rnjB gene significantly attenuates expression of a major virulence factor involved in enterococcal pathogenesis, the Ebp pili...
2017: PloS One
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