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https://www.readbyqxmd.com/read/29458070/the-epigenetic-alterations-of-endogenous-retroelements-in-aging
#1
REVIEW
Maurizio Cardelli
Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent discoveries demonstrate that these mobile genetic elements not only act as intragenomic parasites, but also exert regulatory roles in living cells. The risk of genomic instability represented by endogenous retroelements is normally counteracted by a series of epigenetic control mechanisms which include, among the most important, CpG DNA methylation...
February 16, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29449813/non-nucleotide-agonists-triggering-p2x7-receptor-activation-and-pore-formation
#2
REVIEW
Francesco Di Virgilio, Anna L Giuliani, Valentina Vultaggio-Poma, Simonetta Falzoni, Alba C Sarti
The P2X7 receptor (P2X7R) is a ligand-gated plasma membrane ion channel belonging to the P2X receptor subfamily activated by extracellular nucleotides. General consensus holds that the physiological (and maybe the only) agonist is ATP. However, scattered evidence generated over the last several years suggests that ATP might not be the only agonist, especially at inflammatory sites. Solid data show that NAD + covalently modifies the P2X7R of mouse T lymphocytes, thus lowering the ATP threshold for activation...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29425681/differences-in-the-internalization-of-self-inactivating-vsvg-pseudotyped-murine-leukemia-virus-based-vectors-in-human-and-murine-cells
#3
Mónica Loreto Acevedo, Francisco García-de Gracia, Camila Miranda-Cárdenas, Ricardo Soto-Rifo, Francisco Aguayo, Oscar León
Self-inactivating VSVG-pseudotyped murine leukemia virus (SIN-VSVG-MLV) has been widely used to generate stable cell lines and produce gene delivery vectors. Despite the broad cellular tropism of the VSVG-pseudotyped MLV, we observed differential viral transduction efficiency depending on the host cell type used. In order to determine the mechanism underlying these differences, we used a GFP-expressing SIN-VSVG-MLV and analyzed the major steps of viral transduction in different cell lines including human epithelial, T-lymphocytes, monocytes and murine fibroblast cells...
February 6, 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/29395326/breaching-self-tolerance-to-alu-duplex-rna-underlies-mda5-mediated-inflammation
#4
Sadeem Ahmad, Xin Mu, Fei Yang, Emily Greenwald, Ji Woo Park, Etai Jacob, Cheng-Zhong Zhang, Sun Hur
Aberrant activation of innate immune receptors can cause a spectrum of immune disorders, such as Aicardi-Goutières syndrome (AGS). One such receptor is MDA5, a viral dsRNA sensor that induces antiviral immune response. Using a newly developed RNase-protection/RNA-seq approach, we demonstrate here that constitutive activation of MDA5 in AGS results from the loss of tolerance to cellular dsRNAs formed by Alu retroelements. While wild-type MDA5 cannot efficiently recognize Alu-dsRNAs because of its limited filament formation on imperfect duplexes, AGS variants of MDA5 display reduced sensitivity to duplex structural irregularities, assembling signaling-competent filaments on Alu-dsRNAs...
January 8, 2018: Cell
https://www.readbyqxmd.com/read/29395325/human-adar1-prevents-endogenous-rna-from-triggering-translational-shutdown
#5
Hachung Chung, Jorg J A Calis, Xianfang Wu, Tony Sun, Yingpu Yu, Stephanie L Sarbanes, Viet Loan Dao Thi, Abigail R Shilvock, H-Heinrich Hoffmann, Brad R Rosenberg, Charles M Rice
Type I interferon (IFN) is produced when host sensors detect foreign nucleic acids, but how sensors differentiate self from nonself nucleic acids, such as double-stranded RNA (dsRNA), is incompletely understood. Mutations in ADAR1, an adenosine-to-inosine editing enzyme of dsRNA, cause Aicardi-Goutières syndrome, an autoinflammatory disorder associated with spontaneous interferon production and neurologic sequelae. We generated ADAR1 knockout human cells to explore ADAR1 substrates and function. ADAR1 primarily edited Alu elements in RNA polymerase II (pol II)-transcribed mRNAs, but not putative pol III-transcribed Alus...
January 12, 2018: Cell
https://www.readbyqxmd.com/read/29386205/liver-x-receptor-binding-dna-motif-associated-with-atherosclerosis-specific-dna-methylation-profiles-of-alu-elements-and-neighboring-cpg-islands
#6
Fabiola E Tristán-Flores, Plinio Guzmán, Melany S Ortega-Kermedy, Gabriela Cruz-Torres, Carmen de la Rocha, Guillermo A Silva-Martínez, Dalia Rodríguez-Ríos, Yolanda Alvarado-Caudillo, Gloria Barbosa-Sabanero, Sergi Sayols, Gertrud Lund, Silvio Zaina
BACKGROUND: The signals that determine atherosclerosis-specific DNA methylation profiles are only partially known. We previously identified a 29-bp DNA motif (differential methylation motif [DMM]) proximal to CpG islands (CGIs) that undergo demethylation in advanced human atheromas. Those data hinted that the DMM docks modifiers of DNA methylation and transcription. METHODS AND RESULTS: We sought to functionally characterize the DMM. We showed that the DMM overlaps with the RNA polymerase III-binding B box of Alu short interspersed nuclear elements and contains a DR2 nuclear receptor response element...
January 31, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29385530/integrative-transcriptome-sequencing-reveals-extensive-alternative-trans-splicing-and-cis-backsplicing-in-human-cells
#7
Trees-Juen Chuang, Yen-Ju Chen, Chia-Ying Chen, Te-Lun Mai, Yi-Da Wang, Chung-Shu Yeh, Min-Yu Yang, Yu-Ting Hsiao, Tien-Hsien Chang, Tzu-Chien Kuo, Hsin-Hua Cho, Chia-Ning Shen, Hung-Chih Kuo, Mei-Yeh Lu, Yi-Hua Chen, Shan-Chi Hsieh, Tai-Wei Chiang
Transcriptionally non-co-linear (NCL) transcripts can originate from trans-splicing (trans-spliced RNA; 'tsRNA') or cis-backsplicing (circular RNA; 'circRNA'). While numerous circRNAs have been detected in various species, tsRNAs remain largely uninvestigated. Here, we utilize integrative transcriptome sequencing of poly(A)- and non-poly(A)-selected RNA-seq data from diverse human cell lines to distinguish between tsRNAs and circRNAs. We identified 24,498 NCL events and found that a considerable proportion (20-35%) of them arise from both tsRNAs and circRNAs, representing extensive alternative trans-splicing and cis-backsplicing in human cells...
January 27, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29363428/a-survey-on-cellular-rna-editing-activity-in-response-to-candida-albicans-infections
#8
Yaowei Huang, Yingying Cao, Jiarui Li, Yuanhua Liu, Wu Zhong, Xuan Li, Chen Chen, Pei Hao
BACKGROUND: Adenosine-to-Inosine (A-to-I) RNA editing is catalyzed by the adenosine deaminase acting on RNA (ADAR) family of enzymes, which induces alterations in mRNA sequence. It has been shown that A-to-I RNA editing events are of significance in the cell's innate immunity and cellular response to viral infections. However, whether RNA editing plays a role in cellular response to microorganism/fungi infection has not been determined. Candida albicans, one of the most prevalent human pathogenic fungi, usually act as a commensal on skin and superficial mucosal, but has been found to cause candidiasis in immunosuppression patients...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29340213/non-coding-rnas-as-transcriptional-regulators-in-eukaryotes
#9
O Y Burenina, T S Oretskaya, E A Kubareva
Non-coding RNAs up to 1,000 nucleotides in length are widespread in eukaryotes and fulfil various regulatory functions, in particular during chromatin remodeling and cell proliferation. These RNAs are not translated into proteins: thus, they are non-coding RNAs (ncRNAs). The present review describes the eukaryotic ncRNAs involved in transcription regulation, first and foremost, targeting RNA polymerase II (RNAP II) and/or its major proteinaceous transcription factors. The current state of knowledge concerning the regulatory functions of SRA and TAR RNA, 7SK and U1 snRNA, GAS5 and DHFR RNA is summarized herein...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29323137/issues-with-the-specificity-of-immunological-reagents-for-nlrp3-implications-for-age-related-macular-degeneration
#10
Cassandra Kosmidou, Nikolaos E Efstathiou, Mien V Hoang, Shoji Notomi, Eleni K Konstantinou, Masayuki Hirano, Kosuke Takahashi, Daniel E Maidana, Pavlina Tsoka, Lucy Young, Evangelos S Gragoudas, Timothy W Olsen, Yuki Morizane, Joan W Miller, Demetrios G Vavvas
Contradictory data have been presented regarding the implication of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in age-related macular degeneration (AMD), the leading cause of vision loss in the Western world. Recognizing that antibody specificity may explain this discrepancy and in line with recent National Institutes of Health (NIH) guidelines requiring authentication of key biological resources, the specificity of anti-NLRP3 antibodies was assessed to elucidate whether non-immune RPE cells express NLRP3...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29288557/alu-element-insertion-in-pklr-gene-as-a-novel-cause-of-pyruvate-kinase-deficiency-in-middle-eastern-patients
#11
Harry Lesmana, Lisa Dyer, Xia Li, James Denton, Jenna Griffiths, Satheesh Chonat, Katie G Seu, Matthew M Heeney, Kejian Zhang, Robert J Hopkin, Theodosia A Kalfa
Pyruvate kinase deficiency (PKD) is the most frequent red blood cell enzyme abnormality of the glycolytic pathway and the most common cause of hereditary nonspherocytic hemolytic anemia. Over 250 PKLR-gene mutations have been described, including missense/nonsense, splicing and regulatory mutations, small insertions, small and gross deletions, causing PKD and hemolytic anemia of variable severity. Alu retrotransposons are the most abundant mobile DNA sequences in the human genome, contributing to almost 11% of its mass...
December 30, 2017: Human Mutation
https://www.readbyqxmd.com/read/29283313/circular-rnas-are-abundantly-expressed-and-upregulated-during-human-epidermal-stem-cell-differentiation
#12
Lasse Sommer Kristensen, Trine Line Hauge Okholm, Morten Trillingsgaard Venø, Jørgen Kjems
The expression patterns of endogenous circular RNA (circRNA) molecules during epidermal stem cell (EpSC) differentiation have not previously been explored. Here, we show that circRNAs are abundantly expressed in EpSCs and that their expression change dramatically during differentiation in a coordinated manner. Overall, circRNAs are expressed at higher levels in the differentiated cells, and many upregulated circRNAs are derived from developmental genes, including four different circRNAs from DLG1. The observed changes in circRNA expression were largely independent of host gene expression, and circRNAs independently upregulated upon differentiation are more prone to AGO2 binding and have more predicted miRNA binding sites compared to stably expressed circRNAs...
December 28, 2017: RNA Biology
https://www.readbyqxmd.com/read/29234321/viral-impact-in-autoimmune-diseases-expanding-the-x-chromosome-nucleolus-nexus-hypothesis
#13
Wesley H Brooks
Viruses are suspected of significant roles in autoimmune diseases but the mechanisms are unclear. We get some insight by considering demands a virus places on host cells. Viruses not only require production of their own proteins, RNA and/or DNA, but also production of additional cellular machinery, such as ribosomes, to handle the increased demands. Since the nucleolus is a major site of RNA processing and ribonucleoprotein assembly, nucleoli are targeted by viruses, directly when viral RNA and proteins enter the nucleolus and indirectly when viruses induce increased expression of cellular polyamine genes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29219079/computational-identification-of-harmful-mutation-regions-to-the-activity-of-transposable-elements
#14
Lingling Jin, Ian McQuillan, Longhai Li
BACKGROUND: Transposable elements (TEs) are interspersed DNA sequences that can move or copy to new positions within a genome. TEs are believed to promote speciation and their activities play a significant role in human disease. In the human genome, the 22 AluY and 6 AluS TE subfamilies have been the most recently active, and their transposition has been implicated in many inherited human diseases and in various forms of cancer. Therefore, understanding their transposition activity is very important and identifying the factors that affect their transpositional activity is of great interest...
November 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29203771/alu-dependent-rna-editing-of-gli1-promotes-malignant-regeneration-in-multiple-myeloma
#15
Elisa Lazzari, Phoebe K Mondala, Nathaniel Delos Santos, Amber C Miller, Gabriel Pineda, Qingfei Jiang, Heather Leu, Shawn A Ali, Anusha-Preethi Ganesan, Christina N Wu, Caitlin Costello, Mark Minden, Raffaella Chiaramonte, A Keith Stewart, Leslie A Crews, Catriona H M Jamieson
Despite novel therapies, relapse of multiple myeloma (MM) is virtually inevitable. Amplification of chromosome 1q, which harbors the inflammation-responsive RNA editase adenosine deaminase acting on RNA (ADAR)1 gene, occurs in 30-50% of MM patients and portends a poor prognosis. Since adenosine-to-inosine RNA editing has recently emerged as a driver of cancer progression, genomic amplification combined with inflammatory cytokine activation of ADAR1 could stimulate MM progression and therapeutic resistance. Here, we report that high ADAR1 RNA expression correlates with reduced patient survival rates in the MMRF CoMMpass data set...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29176737/cgas-drives-noncanonical-inflammasome-activation-in-age-related-macular-degeneration
#16
Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J Fowler, Elmira Baghdasaryan, Kenneth M Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R Hinton, Norbert Leitinger, John C Cambier, Joseph D Buxbaum, M Cristina Kenney, S Michal Jazwinski, Hiroshi Nagai, Isao Hara, A Phillip West, Katherine A Fitzgerald, SriniVas R Sadda, Bradley D Gelfand, Jayakrishna Ambati
Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion...
November 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29145975/in-cancer-a-to-i-rna-editing-can-be-the-driver-the-passenger-or-the-mechanic
#17
Nabeel S Ganem, Noa Ben-Asher, Ayelet T Lamm
In recent years, A-to-I RNA modifications performed by the Adenosine Deaminase Acting on RNA (ADAR) protein family were found to be expressed at altered levels in multiple human malignancies. A-to-I RNA editing changes adenosine to inosine on double stranded RNA, thereby changing transcript sequence and structure. Although A-to-I RNA editing have the potential to change essential mRNA transcripts, affecting their corresponding protein structures, most of the human editing sites identified to date reside in non-coding repetitive transcripts such as Alu elements...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29103173/a-role-for-the-mutagenic-dna-self-catalyzed-depurination-mechanism-in-the-evolution-of-7sl-derived-rnas
#18
Maxwell P Gold, Jacques R Fresco
The Alu element, the most prevalent SINE (short interspersed element) in the human genome, is one of the many RNA-encoding genes that evolved from the 7SL RNA gene. During analysis of the evolution of 7SL-derived RNAs, two distinct evolutionary intermediates capable of self-catalyzed DNA depurination (SDP) were identified. These SDP sequences spontaneously create apurinic sites that can result in increased mutagenesis due to their error-prone repair. This DNA self-depurination mechanism has been shown both in vitro and in vivo to lead to substitution and short frameshift mutations at a frequency that far exceeds their occurrence due to random errors in DNA replication...
October 2017: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/28991230/alu-rna-accumulation-induces-epithelial-to-mesenchymal-transition-by-modulating-mir-566-and-is-associated-with-cancer-progression
#19
F Di Ruocco, V Basso, M Rivoire, P Mehlen, J Ambati, S De Falco, V Tarallo
Alu sequences are the most abundant short interspersed repeated elements in the human genome. Here we show that in a cell culture model of colorectal cancer (CRC) progression, we observe accumulation of Alu RNA that is associated with reduced DICER1 levels. Alu RNA induces epithelial-to-mesenchymal transition (EMT) by acting as a molecular sponge of miR-566. Moreover, Alu RNA accumulates as consequence of DICER1 deficit in colorectal, ovarian, renal and breast cancer cell lines. Interestingly, Alu RNA knockdown prevents DICER1 depletion-induced EMT despite global microRNA (miRNA) downregulation...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28751461/novel-aberrations-uncovered-in-barrett-s-esophagus-and-esophageal-adenocarcinoma-using-whole-transcriptome-sequencing
#20
Jesper L V Maag, Oliver M Fisher, Angelique Levert-Mignon, Dominik C Kaczorowski, Melissa L Thomas, Damian J Hussey, David I Watson, Antony Wettstein, Yuri V Bobryshev, Melanie Edwards, Marcel E Dinger, Reginald V Lord
Esophageal adenocarcinoma (EAC) has one of the fastest increases in incidence of any cancer, along with poor five-year survival rates. Barrett's esophagus (BE) is the main risk factor for EAC; however, the mechanisms driving EAC development remain poorly understood. Here, transcriptomic profiling was performed using RNA-sequencing (RNA-seq) on premalignant and malignant Barrett's tissues to better understand this disease. Machine-learning and network analysis methods were applied to discover novel driver genes for EAC development...
July 27, 2017: Molecular Cancer Research: MCR
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