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Rna degradation

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https://www.readbyqxmd.com/read/28634583/circular-rnas-biogenesis-function-and-role-in-human-diseases
#1
REVIEW
John Greene, Anne-Marie Baird, Lauren Brady, Marvin Lim, Steven G Gray, Raymond McDermott, Stephen P Finn
Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28634288/qsva-framework-for-rna-quality-correction-in-differential-expression-analysis
#2
Andrew E Jaffe, Ran Tao, Alexis L Norris, Marc Kealhofer, Abhinav Nellore, Joo Heon Shin, Dewey Kim, Yankai Jia, Thomas M Hyde, Joel E Kleinman, Richard E Straub, Jeffrey T Leek, Daniel R Weinberger
RNA sequencing (RNA-seq) is a powerful approach for measuring gene expression levels in cells and tissues, but it relies on high-quality RNA. We demonstrate here that statistical adjustment using existing quality measures largely fails to remove the effects of RNA degradation when RNA quality associates with the outcome of interest. Using RNA-seq data from molecular degradation experiments of human primary tissues, we introduce a method-quality surrogate variable analysis (qSVA)-as a framework for estimating and removing the confounding effect of RNA quality in differential expression analysis...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28634160/high-throughput-characterization-of-cascade-type-i-e-crispr-guide-efficacy-reveals-unexpected-pam-diversity-and-target-sequence-preferences
#3
Becky Xu Hua Fu, Michael Wainberg, Anshul Kundaje, Andrew Z Fire
Interactions between Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs and CRISPR-associated (Cas) proteins form an RNA-guided adaptive immune system in prokaryotes. The adaptive immune system utilizes segments of the genetic material of invasive foreign elements in the CRISPR locus. The loci are transcribed and processed to produce small CRISPR RNAs (crRNAs), with degradation of invading genetic material directed by a combination of complementarity between RNA and DNA and in some cases recognition of adjacent motifs called PAMs (Protospacer Adjacent Motifs)...
June 20, 2017: Genetics
https://www.readbyqxmd.com/read/28629934/recent-advances-in-leishmania-reverse-genetics-manipulating-a-manipulative-parasite
#4
REVIEW
Samuel M Duncan, Nathaniel G Jones, Jeremy C Mottram
In this review we describe the expanding repertoire of molecular tools with which to study gene function in Leishmania. Specifically we review the tools available for studying functions of essential genes, such as plasmid shuffle and DiCre, as well as the rapidly expanding portfolio of available CRISPR/Cas9 approaches for large scale gene knockout and endogenous tagging. We include detail on approaches that allow the direct manipulation of RNA using RNAi and protein levels via Tet or DiCre induced overexpression and destabilization domain mediated degradation...
June 16, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28628737/analysis-of-structure-activity-relationships-based-on-the-hcv-sliib-ires-rna-targeting-gghyrfk-cu-complex
#5
Martin J Ross, Insiya Fidai, James Allan Cowan
New therapeutics for the targeting of the hepatitis C virus have been released in recent years. Although these therapies are less prone to resistance, they are still administered in cocktails as a combination of drugs targeting various aspects of the viral life cycle. Herein, we aim to contribute to an arsenal of new HCV therapeutics by targeting HCV internal ribosomal entry sequence (IRES) RNA via development of catalytic metallodrugs that function to degrade rather than inhibit the target molecule. Based on a previously characterized HCV IRES stem-loop IIb RNA-targeting metallopeptide Cu-GGHYrFK (1-Cu), an all L-analogue (3-Cu) and a series of additional complexes with single alanine substitutions in the targeting domain were prepared and screened to determine the influence each amino acid side-chain on RNA localization and recognition, and catalytic reactivity toward the RNA...
June 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28628654/the-apah-like-phosphatase-tbalph1-is-the-major-mrna-decapping-enzyme-of-trypanosomes
#6
Susanne Kramer
5'-3' decay is the major mRNA decay pathway in many eukaryotes, including trypanosomes. After deadenylation, mRNAs are decapped by the nudix hydrolase DCP2 of the decapping complex and finally degraded by the 5'-3' exoribonuclease. Uniquely, trypanosomes lack homologues to all subunits of the decapping complex, while deadenylation and 5'-3' degradation are conserved. Here, I show that the parasites use an ApaH-like phosphatase (ALPH1) as their major mRNA decapping enzyme. The protein was recently identified as a novel trypanosome stress granule protein and as involved in mRNA binding...
June 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28628606/splicing-stimulates-sirna-formation-at-drosophila-dna-double-strand-breaks
#7
Karin Merk, Marco Breinig, Romy Böttcher, Stefan Krebs, Helmut Blum, Michael Boutros, Klaus Förstemann
DNA double-strand breaks trigger the production of locus-derived siRNAs in fruit flies, human cells and plants. At least in flies, their biogenesis depends on active transcription running towards the break. Since siRNAs derive from a double-stranded RNA precursor, a major question is how broken DNA ends can generate matching sense and antisense transcripts. We performed a genome-wide RNAi-screen in cultured Drosophila cells, which revealed that in addition to DNA repair factors, many spliceosome components are required for efficient siRNA generation...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28627704/matrix-metalloproteinase-2-and-9-contribute-to-functional-integrity-and-noise%C3%A2-induced-damage-to-the-blood-labyrinth-barrier
#8
Jun Wu, Weiju Han, Xingrui Chen, Weiwei Guo, Ke Liu, Ruoya Wang, Jishuai Zhang, Na Sai
The cochlear blood-labyrinth barrier (BLB), located in the stria vascularis, is critical for the homeostasis of cochlear solutes and ion transport. Significant disruption to the BLB occurs early during noise‑induced hearing loss. Matrix metalloproteinase (MMP)‑2 and ‑9 are important molecules known to be capable of degrading tight junction (TJ) proteins. The TJ proteins are important components of the extracellular matrix (ECM), required to maintain BLB integrity and permeability. Previous studies have demonstrated that MMP‑2 and ‑9, rich in healthy cochlea, serve an essential role in regulating the cochlear response to acoustic trauma...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627653/mir-543-functions-as-a-tumor-suppressor-in-glioma-in-vitro-and-in-vivo
#9
Liang Xu, Ju Yu, Zhongyong Wang, Qing Zhu, Wenjie Wang, Qing Lan
Gliomas are the most common primary central nervous system tumors and account for approximately 80% of malignant brain tumors. MicroRNAs (miRNAs) are a class of small non-coding, regulatory RNA molecules that mediate the expression levels of specific proteins. As a member of the miRNA family, miR-543 plays a tumor suppressive or an oncogenic role in different types of tumors. However, the expression and role of miR-543 in glioma remain unknown. In the present study, the expression level of miR-543 in glioma cell lines and tissues was investigated...
June 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627618/hypoxia-inducible-factor-1%C3%AE-regulates-autophagy-via-the-p27-e2f1-signaling-pathway
#10
Pan Wang, Meijing Long, Shijie Zhang, Zhenyun Cheng, Xin Zhao, Fucheng He, Hongchun Liu, Liang Ming
Autophagy is a highly conserved process by which the cell contents are delivered to lysosomes for degradation, or are used to provide macromolecules for energy generation under conditions of nutritional starvation. It has previously been demonstrated that cancer cells in hypoxic regions, with an oxygen concentration below the normal physiological level, express hypoxia inducible factor (HIF)‑1α, in order to adapt and survive. HIF‑1α is important in the regulation of oxygen homeostasis and the transcription of hundreds of genes in response to conditions of hypoxia, hence maintaining energy and redox homeostasis...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626931/insecticide-resistance-and-intracellular-proteases
#11
REVIEW
Richard M Wilkins
Pesticide resistance is an example of evolution in action with mechanisms of resistance arising from mutations or increased expression of intrinsic genes. Intracellular proteases have a key role in maintaining healthy cells and in responding to stressors such as pesticides. Insecticide resistant insects have constitutively elevated intracellular protease activity when compared to corresponding susceptible strains. This increase was shown for some cases originally through biochemical enzyme studies and subsequently putatively by transcriptomics and proteomics methods...
June 19, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28626026/protein-kinase-c%C3%AE-activates-fat-mass-and-obesity-associated-protein-by-influencing-its-ubiquitin-proteasome-degradation
#12
Haoran Tai, Xiaobo Wang, Jiao Zhou, Xiaojuan Han, Tingting Fang, Hui Gong, Ning Huang, Honghan Chen, Jianqiong Qin, Ming Yang, Xiawei Wei, Li Yang, Hengyi Xiao
PKCβ is a serine-threonine kinase associated with obesity and diabetic complications; its activation contributes to weight gain, and deletion of its gene results in resistance to genetic- and diet-induced obesity. Fat mass and obesity-associated (FTO) protein is a recently identified RNA demethylase, and its overexpression in mice leads to increased body weight as well as fat mass. Although sharing some features in anabolism regulation, PKCβ and FTO have not been investigated together; therefore, their relationship has not been established...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28626000/baiap3-a-c2-domain-containing-munc13-protein-controls-the-fate-of-dense-core-vesicles-in-neuroendocrine-cells
#13
Xingmin Zhang, Shan Jiang, Kelly A Mitok, Lingjun Li, Alan D Attie, Thomas F J Martin
Dense-core vesicle (DCV) exocytosis is a SNARE (soluble N-ethylmaleimide-sensitive fusion attachment protein receptor)-dependent anterograde trafficking pathway that requires multiple proteins for regulation. Several C2 domain-containing proteins are known to regulate Ca(2+)-dependent DCV exocytosis in neuroendocrine cells. In this study, we identified others by screening all (∼139) human C2 domain-containing proteins by RNA interference in neuroendocrine cells. 40 genes were identified, including several encoding proteins with known roles (CAPS [calcium-dependent activator protein for secretion 1], Munc13-2, RIM1, and SYT10) and many with unknown roles...
June 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28625874/negative-regulation-of-the-rlh-signaling-by-the-e3-ubiquitin-ligase-rnf114
#14
Boren Lin, Qi Ke, Haiying Li, Nichole S Pheifer, David C Velliquette, Douglas W Leaman
The retinoic acid-inducible gene-I (RIG-I)-like helicases (RLH)s are cytoplasmic pattern recognition receptors expressed in both immune and non-immune cells that are essential for detection of intracellular RNA products, primarily of viral origin. Upon binding to viral RNA, RLHs interact with mitochondrial antiviral signaling protein (MAVS) to activate interferon (IFN)-mediated antiviral responses. The RLH/MAVS signaling pathway is regulated by ubiquitination/deubiquitination, in which several ubiquitin-editing proteins play critical roles...
June 15, 2017: Cytokine
https://www.readbyqxmd.com/read/28624615/cell-size-dependent-transcription-of-flc-and-its-antisense-long-non-coding-rna-coolair-explain-cell-to-cell-expression-variation
#15
Robert Ietswaart, Stefanie Rosa, Zhe Wu, Caroline Dean, Martin Howard
Single-cell quantification of transcription kinetics and variability promotes a mechanistic understanding of gene regulation. Here, using single-molecule RNA fluorescence in situ hybridization and mathematical modeling, we dissect cellular RNA dynamics for Arabidopsis FLOWERING LOCUS C (FLC). FLC expression quantitatively determines flowering time and is regulated by antisense (COOLAIR) transcription. In cells without observable COOLAIR expression, we quantify FLC transcription initiation, elongation, intron processing, and lariat degradation, as well as mRNA release from the locus and degradation...
June 8, 2017: Cell Systems
https://www.readbyqxmd.com/read/28624198/emerging-roles-of-circrna-related-to-the-mechanical-stress-in-human-cartilage-degradation-of-osteoarthritis
#16
Qiang Liu, Xin Zhang, Xiaoqing Hu, Lan Yuan, Jin Cheng, Yanfang Jiang, Yingfang Ao
Circular RNAs (circRNAs) are involved in the development of various diseases; however, knowledge on circRNAs in osteoarthritis (OA) is limited. This study aims to identify circRNA expression in different regions affected by OA and to explore the function of mechanical stress-related circRNAs (circRNAs-MSR) in cartilage. Bioinformatics was employed to predict the interaction of circRNAs and mRNAs in the cartilage. Loss-of-function experiments for circRNAs-MSR were performed in vitro. A total of 104 circRNAs were differentially expressed in damaged versus intact cartilage...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28624185/the-formation-of-nanoparticles-between-small-interfering-rna-and-amphipathic-cell-penetrating-peptides
#17
Ly Pärnaste, Piret Arukuusk, Kent Langel, Tanel Tenson, Ülo Langel
Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP and cargo complexes is crucial for understanding the processes related to their delivery. In this study, we used modified analogs of the CPP transportan10 and investigated the binding properties of these CPPs to siRNA, the formation parameters of the CPP/siRNA complexes, and their stabiliy to enzymatic degradation...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28624040/hyperglycemia-attenuates-receptor-activator-of-nf-%C3%AE%C2%BAb-ligand-induced-macrophage-activation-by-suppressing-insulin-signaling
#18
Chitaru Kurihara, Teruyoshi Tanaka, Dai Yamanouchi
BACKGROUND: Although male gender, aging, hypertension, dyslipidemia, and smoking are common risk factors for abdominal aortic aneurysm, diabetes mellitus is an independent negative risk factor. In aneurysm tissue, matrix metalloproteinases (MMPs) expressed by activated macrophages degrades extracellular matrix proteins. In our previous experimental study, we demonstrated that the aneurysmal formation and macrophage activity were suppressed by inhibiting mimicking hyperglycemia (HG) through upregulation of glucose-sensing nuclear receptor, Nr1h2...
June 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28622300/the-als-linked-e102q-mutation-in-sigma-receptor-1-leads-to-er-stress-mediated-defects-in-protein-homeostasis-and-dysregulation-of-rna-binding-proteins
#19
Alice Dreser, Jan Tilmann Vollrath, Antonio Sechi, Sonja Johann, Andreas Roos, Alfred Yamoah, Istvan Katona, Saeed Bohlega, Dominik Wiemuth, Yuemin Tian, Axel Schmidt, Jörg Vervoorts, Marc Dohmen, Cordian Beyer, Jasper Anink, Eleonora Aronica, Dirk Troost, Joachim Weis, Anand Goswami
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28621835/exogenously-applied-dsrna-molecules-deriving-from-zucchini-yellow-mosaic-virus-genome-move-systemically-and-protect-cucurbits-against-zymv
#20
Athanasios Kaldis, Margarita Berbati, Ourania Melita, Chrysavgi Reppa, Maria Holeva, Patricia Otten, Andreas Voloudakis
Zucchini yellow mosaic virus (ZYMV) causes serious damage in a great number of cucurbits and control measures are necessary. Transgenic cucurbits expressing parts of ZYMV genome were shown to be resistant against the cognate virus. A non-transgenic approach involving exogenous application of dsRNA has also been shown to induce resistance in tobacco against cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV). In the present study, dsRNA molecules derived from the helper component-proteinase (HC-Pro) and coat protein (CP) genes of the ZYMV_DE_2014 isolate were produced in vitro...
June 16, 2017: Molecular Plant Pathology
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