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RNA biogenesis

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https://www.readbyqxmd.com/read/27932311/daclatasvir-prevents-hepatitis-c-virus-by-blocking-transfer-of-viral-genome-to-assembly-sites
#1
Bertrand Boson, Solène Denolly, Fanny Turlure, Christophe Chamot, Marlène Dreux, François-Loïc Cosset
BACKGROUND & AIMS: Daclatasvir is a direct-acting antiviral agent and potent inhibitor of NS5A, which is involved in replication of the hepatitis C virus (HCV) genome, presumably via membranous web shaping, and assembly of new virions, likely via transfer of the HCV RNA genome to viral particle assembly sites. Daclatasvir inhibits the formation of new membranous web structures and, ultimately, of replication complex vesicles, but also inhibits an early assembly step. We investigated the relationship between daclatasvir-induced clustering of HCV proteins, intracellular localization of viral RNAs and inhibition of viral particle assembly...
December 5, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27929436/comparison-of-small-rna-profiles-of-glycine-max-and-glycine-soja-at-early-developmental-stages
#2
Yuzhe Sun, Zeta Mui, Xuan Liu, Aldrin Kay-Yuen Yim, Hao Qin, Fuk-Ling Wong, Ting-Fung Chan, Siu-Ming Yiu, Hon-Ming Lam, Boon Leong Lim
Small RNAs, including microRNAs (miRNAs) and phased small interfering RNAs (phasiRNAs; from PHAS loci), play key roles in plant development. Cultivated soybean, Glycine max, contributes a great deal to food production, but, compared to its wild kin, Glycine soja, it may lose some genetic information during domestication. In this work, we analyzed the sRNA profiles of different tissues in both cultivated (C08) and wild soybeans (W05) at three stages of development. A total of 443 known miRNAs and 15 novel miRNAs showed varying abundances between different samples, but the miRNA profiles were generally similar in both accessions...
December 6, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27928054/the-influence-of-the-5-terminal-nucleotide-on-agoshrna-activity-and-biogenesis-importance-of-the-polymerase-iii-transcription-initiation-site
#3
Elena Herrera-Carrillo, Zong-Liang Gao, Alex Harwig, Matthias T Heemskerk, Ben Berkhout
Recent evidence indicates that shRNAs with a relatively short basepaired stem do not require Dicer processing, but instead are processed by the Argonaute 2 protein (Ago2). We named these molecules AgoshRNAs as both their processing and silencing function are mediated by Ago2. This alternative processing yields only a single RNA guide strand, which can avoid off-target effects induced by the passenger strand of regular shRNAs. It is important to understand this alternative processing route in mechanistic detail such that one can design improved RNA reagents...
December 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27927715/chromatin-environment-transcriptional-regulation-and-splicing-distinguish-lincrnas-and-mrnas
#4
Marta Melé, Kaia Mattioli, William Mallard, David M Shechner, Chiara Gerhardinger, John L Rinn
While long intergenic noncoding RNAs (lincRNAs) and mRNAs share similar biogenesis pathways, these transcript classes differ in many regards. LincRNAs are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre- and post-transcriptional regulation is different from that of mRNAs. Here, we perform an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. We find that lincRNA promoters are depleted of transcription factor (TF) binding sites, yet enriched for some specific factors such as GATA and FOS relative to mRNA promoters...
December 7, 2016: Genome Research
https://www.readbyqxmd.com/read/27926991/human-mitochondrial-nucleases
#5
REVIEW
Francesco Bruni, Robert N Lightowlers, Zofia M Chrzanowska-Lightowlers
Mitochondria are cytosolic organelles that have many essential roles including ATP production via oxidative phosphorylation, apoptosis, iron-sulphur cluster biogenesis, heme and steroid synthesis, calcium homeostasis and regulation of cellular redox state. One of the unique features of these organelles is the presence of an extra-chromosomal mitochondrial genome (mtDNA), together with all the machinery required to replicate and transcribe mtDNA. The accurate maintenance of mitochondrial gene expression is essential for correct organellar metabolism, and is in part dependent on the levels of mtDNA and mt-RNA, which are regulated by balancing synthesis against degradation...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27924483/rapid-generation-of-mirna-inhibitor-leads-by-bioinformatics-and-efficient-high-throughput-screening-methods
#6
Christopher L Haga, Sai Pradeep Velagapudi, Jessica L Childs-Disney, Jacqueline Strivelli, Matthew D Disney, Donald G Phinney
The discovery of microRNAs (miRNAs) has opened an entire new avenue for drug development. These short (15-22 nucleotides) noncoding RNAs, which function in RNA silencing and posttranscriptional regulation of gene expression, have been shown to critically affect numerous pathways in both development and disease progression. Current miRNA drug development focuses on either reintroducing the miRNA into cells through the use of a miRNA mimic or inhibiting its function via use of a synthetic antagomir. Although these methods have shown some success as therapeutics, they face challenges particularly with regard to cellular uptake and for use as systemic reagents...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924480/design-of-multimodal-small-molecules-targeting-mirnas-biogenesis-synthesis-and-in-vitro-evaluation
#7
Duc D Vo, Maria Duca
microRNAs (miRNAs) are emerging as novel biological targets for medicinal chemists to develop chemical tools for intracellular regulation. In this context, the discovery of small-molecule drugs targeting specific miRNAs and modulating their production or function represents a very promising approach that could be further developed for targeted therapy in miRNA-related pathologies. Here, we describe the design of multimodal small molecules as RNA ligands targeting DICER-mediated miRNA maturation. The synthesis and the biochemical evaluation as ligands of stem-loop-structured precursor microRNAs (pre-miRNAs) are reported...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924026/tetools-facilitates-big-data-expression-analysis-of-transposable-elements-and-reveals-an-antagonism-between-their-activity-and-that-of-pirna-genes
#8
Emmanuelle Lerat, Marie Fablet, Laurent Modolo, Hélène Lopez-Maestre, Cristina Vieira
Over recent decades, substantial efforts have been made to understand the interactions between host genomes and transposable elements (TEs). The impact of TEs on the regulation of host genes is well known, with TEs acting as platforms of regulatory sequences. Nevertheless, due to their repetitive nature it is considerably hard to integrate TE analysis into genome-wide studies. Here, we developed a specific tool for the analysis of TE expression: TEtools This tool takes into account the TE sequence diversity of the genome, it can be applied to unannotated or unassembled genomes and is freely available under the GPL3 (https://github...
October 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924005/sub1-contacts-the-rna-polymerase-ii-stalk-to-modulate-mrna-synthesis
#9
Miguel Garavís, Noelia González-Polo, Paula Allepuz-Fuster, Jaime Alegrio Louro, Carlos Fernández-Tornero, Olga Calvo
Biogenesis of messenger RNA is critically influenced by the phosphorylation state of the carboxy-terminal domain (CTD) in the largest RNA polymerase II (RNAPII) subunit. Several kinases and phosphatases are required to maintain proper CTD phosphorylation levels and, additionally, several other proteins modulate them, including Rpb4/7 and Sub1. The Rpb4/7 heterodimer, constituting the RNAPII stalk, promote phosphatase functions and Sub1 globally influences CTD phosphorylation, though its mechanism remains mostly unknown...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924000/folate-deficiency-facilitates-recruitment-of-upstream-binding-factor-to-hot-spots-of-dna-double-strand-breaks-of-rrna-genes-and-promotes-its-transcription
#10
Qiu Xie, Caihua Li, Xiaozhen Song, Lihua Wu, Qian Jiang, Zhiyong Qiu, Haiyan Cao, Kaihui Yu, Chunlei Wan, Jianting Li, Feng Yang, Zebing Huang, Bo Niu, Zhengwen Jiang, Ting Zhang
The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923923/antiviral-innate-immune-response-interferes-with-the-formation-of-replication-associated-membrane-structures-induced-by-a-positive-strand-rna-virus
#11
Diede Oudshoorn, Barbara van der Hoeven, Ronald W A L Limpens, Corrine Beugeling, Eric J Snijder, Montserrat Bárcena, Marjolein Kikkert
: Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER)-derived double-membrane vesicles (DMVs) and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27919066/designed-proteins-induce-the-formation-of-nanocage-containing-extracellular-vesicles
#12
Jörg Votteler, Cassandra Ogohara, Sue Yi, Yang Hsia, Una Nattermann, David M Belnap, Neil P King, Wesley I Sundquist
Complex biological processes are often performed by self-organizing nanostructures comprising multiple classes of macromolecules, such as ribosomes (proteins and RNA) or enveloped viruses (proteins, nucleic acids and lipids). Approaches have been developed for designing self-assembling structures consisting of either nucleic acids or proteins, but strategies for engineering hybrid biological materials are only beginning to emerge. Here we describe the design of self-assembling protein nanocages that direct their own release from human cells inside small vesicles in a manner that resembles some viruses...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27918527/induction-and-suppression-of-antiviral-rna-interference-by-influenza-a-virus-in-mammalian-cells
#13
Yang Li, Megha Basavappa, Jinfeng Lu, Shuwei Dong, D Alexander Cronkite, John T Prior, Hans-Christian Reinecker, Paul Hertzog, Yanhong Han, Wan-Xiang Li, Sihem Cheloufi, Fedor V Karginov, Shou-Wei Ding, Kate L Jeffrey
Influenza A virus (IAV) causes annual epidemics and occasional pandemics, and is one of the best-characterized human RNA viral pathogens(1). However, a physiologically relevant role for the RNA interference (RNAi) suppressor activity of the IAV non-structural protein 1 (NS1), reported over a decade ago(2), remains unknown(3). Plant and insect viruses have evolved diverse virulence proteins to suppress RNAi as their hosts produce virus-derived small interfering RNAs (siRNAs) that direct specific antiviral defence(4-7) by an RNAi mechanism dependent on the slicing activity of Argonaute proteins (AGOs)(8,9)...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27916986/pharmacological-modulation-of-lmna-srsf1-dependent-splicing-abrogates-diet-induced-obesity-in-mice
#14
J Santo, C Lopez-Herrera, C Apolit, Y Bareche, L Lapasset, C Chavey, S Capozi, F Mahuteau, R Najman, P Fornarelli, I C Lopez-Mejía, G Béranger, F Casas, E-Z Amri, B Pau, D Scherrer, J Tazi
BAKGROUND/OBJECTIVES: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. Alternative splicing (AS) and/or polyadenylation enable the LMNA gene to express distinct protein isoforms that exert opposing effects on energy metabolism and lifespan. Here we aimed to use the splicing factor SRSF1 that contribute to the production of these different isoforms as a target to uncover new anti-obesity drug. SUBJECTS/METHODS: Small molecules modulating SR protein activity and splicing, were tested for their abilities to interact with SRSF1 and to modulate LMNA (AS)...
December 5, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27913733/identification-of-2-methylthio-cyclic-n6-threonylcarbamoyladenosine-ms2ct6a-as-a-novel-rna-modification-at-position-37-of-trnas
#15
Byeong-Il Kang, Kenjyo Miyauchi, Michal Matuszewski, Gabriel Silveira D'Almeida, Mary Anne T Rubio, Juan D Alfonzo, Kazuki Inoue, Yuriko Sakaguchi, Takeo Suzuki, Elzbieta Sochacka, Tsutomu Suzuki
Transfer RNA modifications play pivotal roles in protein synthesis. N(6)-threonylcarbamoyladenosine (t(6)A) and its derivatives are modifications found at position 37, 3'-adjacent to the anticodon, in tRNAs responsible for ANN codons. These modifications are universally conserved in all domains of life. t(6)A and its derivatives have pleiotropic functions in protein synthesis including aminoacylation, decoding and translocation. We previously discovered a cyclic form of t(6)A (ct(6)A) as a chemically labile derivative of t(6)A in tRNAs from bacteria, fungi, plants and protists...
December 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27913643/biogenesis-and-transcriptional-regulation-of-long-noncoding-rnas-in-the-human-immune-system
#16
REVIEW
Charles F Spurlock, Philip S Crooke, Thomas M Aune
The central dogma of molecular biology states that DNA makes RNA makes protein. Discoveries over the last quarter of a century found that the process of DNA transcription into RNA gives rise to a diverse array of functional RNA species, including genes that code for protein and noncoding RNAs. For decades, the focus has been on understanding how protein-coding genes are regulated to influence protein expression. However, with the completion of the Human Genome Project and follow-up ENCODE data, it is now appreciated that only 2-3% of the genome codes for protein-coding gene exons and that the bulk of the transcribed genome, apart from ribosomal RNAs, is at the level of noncoding RNA genes...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27911719/transcription-by-rna-polymerase-iii-insights-into-mechanism-and-regulation
#17
REVIEW
Tomasz W Turowski, David Tollervey
The highly abundant, small stable RNAs that are synthesized by RNA polymerase III (RNAPIII) have key functional roles, particularly in the protein synthesis apparatus. Their expression is metabolically demanding, and is therefore coupled to changing demands for protein synthesis during cell growth and division. Here, we review the regulatory mechanisms that control the levels of RNAPIII transcripts and discuss their potential physiological relevance. Recent analyses have revealed differential regulation of tRNA expression at all steps on its biogenesis, with significant deregulation of mature tRNAs in cancer cells...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911188/tuning-the-ribosome-the-influence-of-rrna-modification-on-eukaryotic-ribosome-biogenesis-and-function
#18
Katherine E Sloan, Ahmed S Warda, Sunny Sharma, Karl-Dieter Entian, Denis L J Lafontaine, Markus T Bohnsack
Ribosomal RNAs are extensively modified during their transcription and subsequent maturation in the nucleolus, nucleus and cytoplasm. RNA modifications, which are installed either by snoRNA-guided or by stand-alone enzymes, generally stabilise the structure of the ribosome. However, they also cluster at functionally important sites of the ribosome, such as the peptidyltransferase centre and the decoding site, where they facilitate efficient and accurate protein synthesis. The recent identification of sites of substoichiometric 2'-O-methylation and pseudouridylation has overturned the notion that all rRNA modifications are constitutively present on ribosomes, highlighting nucleotide modifications as an important source of ribosomal heterogeneity...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27908532/ram-589-555-a-new-polymerase-1-inhibitor-as-innovative-targeted-treatment-for-multiple-sclerosis
#19
A Achiron, R Zilkha-Falb, R Mashiach, M Gurevich
Targeting Polymerase-1 (POL1) transcription machinery is a new strategy for suppression of multiple sclerosis (MS) disease activity that is based on suppression of ribosomal biogenesis and subsequent activation of apoptosis. We developed an oral POL1 inhibiting compound RAM-589.555, that suppress ribosomal biogenesis as an innovative therapeutic approach to ameliorate MS. RAM-589.555 shows high permeability, specificity to POL1 pathway, ability to induce apoptosis and to inhibit proliferation and viability of activated lymphocytes both in-vitro and in-vivo...
November 17, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27907888/a-novel-role-for-gsk3%C3%AE-as-a-modulator-of-drosha-microprocessor-activity-and-microrna-biogenesis
#20
Claire E Fletcher, Jack D Godfrey, Akifumi Shibakawa, Martin Bushell, Charlotte L Bevan
Regulation of microRNA (miR) biogenesis is complex and stringently controlled. Here, we identify the kinase GSK3β as an important modulator of miR biogenesis at Microprocessor level. Repression of GSK3β activity reduces Drosha activity toward pri-miRs, leading to accumulation of unprocessed pri-miRs and reduction of pre-miRs and mature miRs without altering levels or cellular localisation of miR biogenesis proteins. Conversely, GSK3β activation increases Drosha activity and mature miR accumulation. GSK3β achieves this through promoting Drosha:cofactor and Drosha:pri-miR interactions: it binds to DGCR8 and p72 in the Microprocessor, an effect dependent upon presence of RNA...
October 23, 2016: Nucleic Acids Research
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