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Rna degradation

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https://www.readbyqxmd.com/read/29145644/paf1-and-ctr9-core-components-of-the-paf1-complex-maintain-low-levels-of-telomeric-repeat-containing-rna
#1
Joana Rodrigues, David Lydall
The conserved PAF1 complex (Cdc73, Paf1, Ctr9, Leo1 and Rtf1, in yeast), binds RNA pol II, and affects levels of many RNAs. Although PAF1 is a complex, there is evidence that different components perform different functions. In yeast, Cdc73, Paf1 and Ctr9 maintain normal telomerase RNA (TLC1) levels and affect telomere length. Here we report a new connection between the PAF1 complex and telomere biology. We show that Paf1 and Ctr9 maintain low telomere repeat containing RNA (TERRA) levels while Cdc73, Leo1 and Rtf1 have lesser effects...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29144457/a-ubiquitin-dependent-signalling-axis-specific-for-alkbh-mediated-dna-dealkylation-repair
#2
Joshua R Brickner, Jennifer M Soll, Patrick M Lombardi, Cathrine B Vågbø, Miranda C Mudge, Clement Oyeniran, Renana Rabe, Jessica Jackson, Meagan E Sullender, Elyse Blazosky, Andrea K Byrum, Yu Zhao, Mark A Corbett, Jozef Gécz, Michael Field, Alessandro Vindigni, Geir Slupphaug, Cynthia Wolberger, Nima Mosammaparast
DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29142827/overexpression-of-the-primary-sigma-factor-gene-siga-improved-carotenoid-production-by-corynebacterium-glutamicum-application-to-production-of-%C3%AE-carotene-and-the-non-native-linear-c50-carotenoid-bisanhydrobacterioruberin
#3
Hironori Taniguchi, Nadja A Henke, Sabine A E Heider, Volker F Wendisch
Corynebacterium glutamicum shows yellow pigmentation due to biosynthesis of the C50 carotenoid decaprenoxanthin and its glycosides. This bacterium has been engineered for production of various non-native cyclic C40 and C50 carotenoids such as β-carotene, astaxanthin or sarcinaxanthin. In this study, the effect of modulating gene expression more broadly by overexpression of sigma factor genes on carotenoid production by C. glutamicum was characterized. Overexpression of the primary sigma factor gene sigA improved lycopene production by recombinant C...
June 2017: Metabolic Engineering Communications
https://www.readbyqxmd.com/read/29141136/systemic-mrna-delivery-to-the-lungs-by-functional-polyester-based-carriers
#4
Yunfeng Yan, Hu Xiong, Xinyi Zhang, Qiang Cheng, Daniel John Siegwart
Messenger RNA (mRNA) has recently come into focus as an emerging therapeutic class with great potential for protein replacement therapy, cancer immunotherapy, regenerative medicine, vaccines, and gene editing. However, the lack of effective and safe delivery methods impedes the broad application of mRNA-based therapeutics. Here, we report a robust approach to develop efficient polymeric delivery carriers for mRNA. Lead polyesters were identified by in vitro screening of a 480-member combinatorially modified poly(trimethylolpropane allyl ether-co-suberoyl chloride) library for the delivery of luciferase encoding mRNA (Luc mRNA) to IGROV1 cells...
November 15, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29137254/quaking-5-suppresses-aggressiveness-of-lung-cancer-cells-through-inhibiting-%C3%AE-catenin-signaling-pathway
#5
Xuexia Zhou, Xuebing Li, Cuiyun Sun, Cuijuan Shi, Dan Hua, Lin Yu, Yanjun Wen, Feng Hua, Qian Wang, Qinghua Zhou, Shizhu Yu
Quaking-5 (QKI-5) belongs to the STAR (signal transduction and activation of RNA) family of RNA binding proteins and functions as a tumor suppressor in several human malignancies. In this study, we attempt to elucidate the role of QKI-5 in the pro-metastasis processes of lung cancer (LC) cells and the underlying mechanisms. We confirmed that QKI-5 was decreased in human LC tissues and cell lines, especially in high-metastatic cells. Moreover, QKI expression was positively correlated with LC patients' survival...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136196/analysis-of-the-natively-unstructured-rna-protein-recognition-core-in-the-escherichia-coli-rna-degradosome-and-its-interactions-with-regulatory-rna-hfq-complexes
#6
Heather A Bruce, Dijun Du, Dijana Matak-Vinkovic, Katarzyna J Bandyra, R William Broadhurst, Esther Martin, Frank Sobott, Alexander V Shkumatov, Ben F Luisi
The RNA degradosome is a multi-enzyme assembly that plays a central role in the RNA metabolism of Escherichia coli and numerous other bacterial species including pathogens. At the core of the assembly is the endoribonuclease RNase E, one of the largest E. coli proteins and also one that bears the greatest region predicted to be natively unstructured. This extensive unstructured region, situated in the C-terminal half of RNase E, is punctuated with conserved short linear motifs that recruit partner proteins, direct RNA interactions, and enable association with the cytoplasmic membrane...
November 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29135975/transcriptomic-profiling-of-human-breast-and-melanoma-cells-selected-by-migration-through-narrow-constraints
#7
Dominika A Rudzka, William Clark, Ann Hedley, Gabriela Kalna, Michael F Olson
The metastatic spread of cancer cells is a step-wise process that starts with dissociation from primary tumours and local invasion of adjacent tissues. The ability to invade local tissues is the product of several processes, including degradation of extracellular matrices (ECM) and movement of tumour cells through physically-restricting gaps. To identify properties contributing to tumour cells squeezing through narrow gaps, invasive MDA-MB-231 human breast cancer and MDA-MB-435 human melanoma cells were subjected to three successive rounds of selection using cell culture inserts with highly constraining 3 μm pores...
November 14, 2017: Scientific Data
https://www.readbyqxmd.com/read/29133885/a-conserved-stem-of-the-myxococcus-xanthus-srna-pxr-controls-srna-accumulation-and-multicellular-development
#8
Yuen-Tsu N Yu, Elizabeth Cooper, Gregory J Velicer
The small RNA (sRNA) Pxr negatively controls multicellular fruiting body formation in the bacterium Myxococcus xanthus, inhibiting the transition from growth to development when nutrients are abundant. Like many other prokaryotic sRNAs, Pxr is predicted to fold into three stem loops (SL1-SL3). SL1 and SL2 are highly conserved across the myxobacteria, whereas SL3 is much more variable. SL1 is necessary for the regulatory function of Pxr but the importance of SL3 in this regard is unknown. To test for cis genetic elements required for Pxr function, we deleted the entire pxr gene from a developmentally defective strain that fails to remove Pxr-mediated blockage of development and reintroduced variably truncated fragments of the pxr region to test for their ability to block development...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133371/turnip-mosaic-virus-counteracts-selective-autophagy-of-the-viral-silencing-suppressor-hcpro
#9
Anders Hafrén, Suayib Üstün, Anton Hochmuth, Steingrim Svenning, Terje Johansen, Daniel Hofius
Autophagy is a conserved intracellular degradation pathway and has emerged as a key mechanism of antiviral immunity in metazoans, including the selective elimination of viral components. In turn, some animal viruses are able to escape and modulate autophagy for enhanced pathogenicity. Whether host autophagic responses and viral countermeasures play similar roles in plant-virus interactions is not well understood. Here, we have identified selective autophagy as antiviral pathway during plant infection with turnip mosaic virus (TuMV), a positive-stranded RNA potyvirus...
November 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29133129/hbsag-mrna-degradation-induced-by-dihydroquinolizinone-molecule-depends-on-hbv-posttranscriptional-regulatory-element
#10
Tianlun Zhou, Timothy Block, Fei Liu, Andrew S Kondratowicz, Liren Sun, Siddhartha Rawat, Jeffrey Branson, Fang Guo, Hongyan Liang, Lauren Bailey, Chris Moore, Xiaohe Wang, Andy Cuconatti, Min Gao, Amy C H Lee, Troy Harasym, Tim Chiu, Dimitar Gotchev, Bruce Dorsey, Rene Rijnbrand, Michael J Sofia
In pursuit of novel therapeutics targeting the hepatitis B virus (HBV) infection, we evaluated a dihydroquinolizinone compound (DHQ-1) that possessed nanomolar activities against the production of virion and surface protein (HBsAg) in tissue culture. This compound also showed broad HBV genotype coverage and was inactive against a panel of DNA and RNA viruses of other species. Oral administration of DHQ-1 in the AAV-HBV mouse model resulted in a strong reduction of serum HBsAg as soon as 4 days following the commencement of treatment...
November 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29131164/an-improved-ms2-system-for-accurate-reporting-of-the-mrna-life-cycle
#11
Evelina Tutucci, Maria Vera, Jeetayu Biswas, Jennifer Garcia, Roy Parker, Robert H Singer
The MS2-MCP system enables researchers to image multiple steps of the mRNA life cycle with high temporal and spatial resolution. However, for short-lived mRNAs, the tight binding of the MS2 coat protein (MCP) to the MS2 binding sites (MBS) protects the RNA from being efficiently degraded, and this confounds the study of mRNA regulation. Here, we describe a reporter system (MBSV6) with reduced affinity for the MCP, which allows mRNA degradation while preserving single-molecule detection determined by single-molecule FISH (smFISH) or live imaging...
November 13, 2017: Nature Methods
https://www.readbyqxmd.com/read/29131148/structure-guided-chemical-modification-of-guide-rna-enables-potent-non-viral-in-vivo-genome-editing
#12
Hao Yin, Chun-Qing Song, Sneha Suresh, Qiongqiong Wu, Stephen Walsh, Luke Hyunsik Rhym, Esther Mintzer, Mehmet Fatih Bolukbasi, Lihua Julie Zhu, Kevin Kauffman, Haiwei Mou, Alicia Oberholzer, Junmei Ding, Suet-Yan Kwan, Roman L Bogorad, Timofei Zatsepin, Victor Koteliansky, Scot A Wolfe, Wen Xue, Robert Langer, Daniel G Anderson
Efficient genome editing with Cas9-sgRNA in vivo has required the use of viral delivery systems, which have limitations for clinical applications. Translational efforts to develop other RNA therapeutics have shown that judicious chemical modification of RNAs can improve therapeutic efficacy by reducing susceptibility to nuclease degradation. Guided by the structure of the Cas9-sgRNA complex, we identify regions of sgRNA that can be modified while maintaining or enhancing genome-editing activity, and we develop an optimal set of chemical modifications for in vivo applications...
November 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29130202/optimizing-molecular-beacons-for-intracellular-analysis-of-rna
#13
Mingming Chen, Yantao Yang, Christopher J Krueger, Antony K Chen
Conventional molecular beacons (MBs) have been used extensively for imaging specific endogenous RNAs in living cells, but their tendency to generate false-positive signals as a result of nuclease degradation and/or nonspecific binding limits sensitive and accurate imaging of intracellular RNAs. In an attempt to overcome this limitation, MBs have been synthesized with various chemically modified oligonucleotide backbones to confer greater biostability. We have recently developed a new MB architecture composed of 2'-O-methyl RNA (2Me), a fully phosphorothioate (PS) modified loop domain and a phosphodiester stem (2Me/PSLOOP MB)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29129707/apobec3b-edits-hbv-dna-and-inhibits-hbv-replication-during-reverse-transcription
#14
Yanmeng Chen, Jie Hu, Xuefei Cai, Yao Huang, Xing Zhou, Zeng Tu, Jieli Hu, John E Tavis, Ni Tang, Ailong Huang, Yuan Hu
Hepatitis B virus is a partially double-stranded DNA virus that replicates by reverse transcription, which occurs within viral core particles in the cytoplasm. The cytidine deaminase APOBEC3B is a cellular restriction factor for HBV. Recently, it was reported that APOBEC3B can edit HBV cccDNA in the nucleus, causing its degradation. However, whether and how it can edit HBV core-associated DNAs during reverse transcription is unclear. Our studies to address this question revealed the following: First, silencing endogenous APOBEC3B in an HBV infection system lead to upregulation of HBV replication...
November 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29128743/the-suppression-of-premature-termination-codons-and-the-repair-of-splicing-mutations-in-cftr
#15
REVIEW
Yifat S Oren, Iwona M Pranke, Batsheva Kerem, Isabelle Sermet-Gaudelus
Premature termination codons (PTC) originate from nucleotide substitution introducing an in-frame PTC. They induce truncated, usually non-functional, proteins, degradation of the PTC containing transcripts by the nonsense-mediated decay (NMD) pathway and abnormal exon skipping. Readthrough compounds facilitate near cognate amino-acyl-tRNA incorporation, leading potentially to restoration of a functional full-length protein. Splicing mutations can lead to aberrantly spliced transcripts by creating a cryptic splice site or destroying a normal site...
November 9, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29128684/mapk-p38-regulates-inflammatory-gene-expression-via-tristetraprolin-doing-good-by-stealth
#16
J D O'Neil, A J Ammit, A R Clark
Tristetraprolin (TTP) is an RNA-destabilizing protein that exerts profound anti-inflammatory effects by inhibiting the expression of tumour necrosis factor and many other inflammatory mediators. The mitogen-activated protein kinase (MAPK) p38 signaling pathway controls the strength and duration of inflammatory responses by regulating both the expression and function of TTP. The kinase MK2 (MAPK activated kinase 2) is activated by MAPK p38, and in turn phosphorylates TTP at two critical serine residues. One consequence of these phosphorylations is the protection of TTP from proteasome-mediated degradation...
November 8, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29128292/profiling-5-tolyltriazole-biodegrading-sludge-communities-using-next-generation-sequencing-and-denaturing-gradient-gel-electrophoresis
#17
Bastian Herzog, Andreas Dötsch, Hilde Lemmer, Harald Horn, Elisabeth Müller
Efficient biodegradation of 5-tolyltriazole (5-TTri) in wastewater treatment would minimize its potential detrimental effects on aquatic systems. Therefore, in order to profile 5-TTri biodegrading activated sludge communities (ASC) by DGGE and NGS, acclimation experiments with (i) easily degradable substrates, and (ii) various complex substrates mimicking wastewater conditions were performed. DGGE revealed four genera: Aminobacter (family Phyllobacteriaceae), Flavobacterium (family Flavobacteriaceae), Pseudomonas (family Pseudomonaceae), and Hydrogenophaga (family Comamonadaceae)...
November 3, 2017: Systematic and Applied Microbiology
https://www.readbyqxmd.com/read/29127284/a-thermostable-cas9-with-increased-lifetime-in-human-plasma
#18
Lucas B Harrington, David Paez-Espino, Brett T Staahl, Janice S Chen, Enbo Ma, Nikos C Kyrpides, Jennifer A Doudna
CRISPR-Cas9 is a powerful technology that has enabled genome editing in a wide range of species. However, the currently developed Cas9 homologs all originate from mesophilic bacteria, making them susceptible to degradation and unsuitable for applications requiring cleavage at elevated temperatures. Here, we show that the Cas9 protein from the thermophilic bacterium Geobacillus stearothermophilus (GeoCas9) catalyzes RNA-guided DNA cleavage at elevated temperatures. GeoCas9 is active at temperatures up to 70 °C, compared to 45 °C for Streptococcus pyogenes Cas9 (SpyCas9), which expands the temperature range for CRISPR-Cas9 applications...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29127149/regnase-1-and-roquin-nonredundantly-regulate-th1-differentiation-causing-cardiac-inflammation-and-fibrosis
#19
Xiaotong Cui, Takashi Mino, Masanori Yoshinaga, Yoshinari Nakatsuka, Fabian Hia, Daichi Yamasoba, Tohru Tsujimura, Keizo Tomonaga, Yutaka Suzuki, Takuya Uehata, Osamu Takeuchi
Regnase-1 and Roquin are RNA binding proteins that are essential for degradation of inflammatory mRNAs and maintenance of immune homeostasis. Although deficiency of either of the proteins leads to enhanced T cell activation, their functional relationship in T cells has yet to be clarified because of lethality upon mutation of both Regnase-1 and Roquin. By using a Regnase-1 conditional allele, we show that mutations of both Regnase-1 and Roquin in T cells leads to massive lymphocyte activation. In contrast, mutation of either Regnase-1 or Roquin affected T cell activation to a lesser extent than the double mutation, indicating that Regnase-1 and Roquin function nonredundantly in T cells...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29126629/characterization-of-innate-responses-induced-by-in-ovo-administration-of-encapsulated-and-free-forms-of-ligands-of-toll-like-receptor-4-and-21-in-chicken-embryos
#20
Jegarubee Bavananthasivam, Tamiru N Alkie, Ayumi Matsuyama-Kato, Douglas C Hodgins, Shayan Sharif
Toll-like receptors (TLRs) are a family of innate receptors that recognize pathogen-associated molecular patterns, including double-stranded RNA, CpG DNA and lipopolysaccharide (LPS). After interaction with their ligands, TLRs initiate innate responses that are manifested by activating cells and inducing expression of cytokines that help mediate adaptive immune responses. TLR ligands (TLR-Ls) have the potential to be used prophylactically (alone) or as vaccine adjuvants to promote host immunity. Encapsulating TLR-Ls in nanoparticles, such as Poly (d,l-lactic-co-glycolic acid), may prolong responses through sustained release of the ligands...
October 25, 2017: Research in Veterinary Science
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