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https://www.readbyqxmd.com/read/28185365/circrnas-biogenesis-properties-roles-and-their-relationships-with-liver-diseases-running-title-circular-rnas-and-liver-diseases
#1
REVIEW
Ting Yao, Qingqing Chen, Liyun Fu, Junming Guo
Circular RNAs (circRNAs) are a class of new found RNA molecules that have a special covalent loop structure without 5' cap and 3' tail. Researchers have found that circRNAs may be generated by intron-pairing-driven or lariat-driven circularization. They are cleared up via extracellular vesicles. They have some advantages such as stable, conservation, tissue specificity and so on. By severing as sponge of microRNAs, interacting with long non-coding RNAs, mRNA, or proteins, circRNAs regulate gene expression at transcriptional and post-transcriptional levels and contribute carcinogenesis...
February 10, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28159804/lariat-capping-as-a-tool-to-study-5-cap-functions-of-individual-yeast-mrna-species-in-vivo
#2
Nicolai Krogh, Max Pietschmann, Manfred Schmid, Torben Heick Jensen, Henrik Nielsen
The 5' cap structure of eukaryotic mRNA is critical for its processing, transport, translation and stability. The many functions of the cap and the fact that most, if not all, mRNA carries the same type of cap makes it difficult to analyse cap function in vivo at individual steps of gene expression. We have used the lariat capping ribozyme (LCrz) from the myxomycete Didymium to replace the mRNA m7G cap of a single reporter mRNA species with a tiny lariat in which the first and the third nucleotide are joined by a 2', 5' phosphodiester bond...
February 3, 2017: RNA
https://www.readbyqxmd.com/read/28119336/large-scale-analysis-of-branchpoint-usage-across-species-and-cell-lines
#3
Allison J Taggart, Chien-Ling Lin, Barsha Shrestha, Claire Heintzelman, Seongwon Kim, William G Fairbrother
The coding sequence of each human pre-mRNA is interrupted, on average, by eleven introns that must be spliced out for proper gene expression. Each intron contains three obligate signals: a 5' splice site, a branch site and a 3' splice site. Splice site usage has been mapped exhaustively across different species, cell types and cellular states. In contrast, only a small fraction of branch sites have been identified even once. The few reported annotations of branch site are imprecise as reverse transcriptase skips several nucleotides while traversing a 2-5 linkage...
January 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28076345/structure-of-a-spliceosome-remodelled-for-exon-ligation
#4
Sebastian M Fica, Chris Oubridge, Wojciech P Galej, Max E Wilkinson, Xiao-Chen Bai, Andrew J Newman, Kiyoshi Nagai
The spliceosome excises introns from pre-mRNAs in two sequential transesterifications-branching and exon ligation-catalysed at a single catalytic metal site in U6 small nuclear RNA (snRNA). Recently reported structures of the spliceosomal C complex with the cleaved 5' exon and lariat-3'-exon bound to the catalytic centre revealed that branching-specific factors such as Cwc25 lock the branch helix into position for nucleophilic attack of the branch adenosine at the 5' splice site. Furthermore, the ATPase Prp16 is positioned to bind and translocate the intron downstream of the branch point to destabilize branching-specific factors and release the branch helix from the active site...
February 16, 2017: Nature
https://www.readbyqxmd.com/read/28055181/fluorescent-branched-rnas-for-high-throughput-analysis-of-dbr1-enzyme-kinetics-and-inhibition
#5
Adam Katolik, Nathaniel E Clark, Nobuhiro Tago, Eric J Montemayor, P John Hart, Masad J Damha
We have developed fluorescent 2',5' branched RNAs (bRNA) that permit real time monitoring of RNA lariat (intron) debranching enzyme (Dbr1) kinetics. These compounds contain fluorescein (FAM) on the 5' arm of the bRNA that is quenched by a dabcyl moiety on the 2' arm. Dbr1-mediated hydrolysis of the 2',5' linkage induces a large increase in fluorescence, providing a convenient assay for Dbr1 hydrolysis. We show that unlabeled bRNAs with non-native 2',5'-phosphodiester linkages, such as phosphoramidate or phosphorothioate, can inhibit Dbr1-mediated debranching with IC50 values in the low nanomolar range...
January 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28053119/short-intron-derived-ncrnas
#6
Florent Hubé, Damien Ulveling, Alain Sureau, Sabrina Forveille, Claire Francastel
Introns represent almost half of the human genome, although they are eliminated from transcripts through RNA splicing. Yet, different classes of non-canonical miRNAs have been proposed to originate directly from intron splicing. Here, we considered the alternative splicing of introns as an interesting source of miRNAs, compatible with a developmental switch. We report computational prediction of new Short Intron-Derived ncRNAs (SID), defined as precursors of smaller ncRNAs like miRNAs and snoRNAs produced directly by splicing, and tested their dependence on each key factor in canonical or alternative miRNAs biogenesis (Drosha, DGCR8, DBR1, snRNP70, U2AF65, PRP8, Dicer, Ago2)...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27980089/structure-of-a-yeast-step-ii-catalytically-activated-spliceosome
#7
Chuangye Yan, Ruixue Wan, Rui Bai, Gaoxingyu Huang, Yigong Shi
Each cycle of precursor messenger RNA (pre-mRNA) splicing comprises two sequential reactions, first freeing the 5' exon and generating an intron lariat-3' exon and then ligating the two exons and releasing the intron lariat. The second reaction is executed by the step II catalytically activated spliceosome (known as the C* complex). Here, we present the cryo-electron microscopy structure of a C* complex from Saccharomyces cerevisiae at an average resolution of 4.0 angstroms. Compared with the preceding spliceosomal complex (C complex), the lariat junction has been translocated by 15 to 20 angstroms to vacate space for the incoming 3'-exon sequences...
January 13, 2017: Science
https://www.readbyqxmd.com/read/27940559/functional-link-between-deah-rha-helicase-prp43-activation-and-atp-base-binding
#8
Julien Robert-Paganin, Maral Halladjian, Magali Blaud, Simon Lebaron, Lila Delbos, Florian Chardon, Régine Capeyrou, Odile Humbert, Yves Henry, Anthony K Henras, Stéphane Réty, Nicolas Leulliot
The DEAH box helicase Prp43 is a bifunctional enzyme from the DEAH/RHA helicase family required both for the maturation of ribosomes and for lariat intron release during splicing. It interacts with G-patch domain containing proteins which activate the enzymatic activity of Prp43 in vitro by an unknown mechanism. In this work, we show that the activation by G-patch domains is linked to the unique nucleotide binding mode of this helicase family. The base of the ATP molecule is stacked between two residues, R159 of the RecA1 domain (R-motif) and F357 of the RecA2 domain (F-motif)...
December 9, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27934709/crystal-structures-of-a-group-ii-intron-lariat-primed-for-reverse-splicing
#9
Maria Costa, Hélène Walbott, Dario Monachello, Eric Westhof, François Michel
The 2'-5' branch of nuclear premessenger introns is believed to have been inherited from self-splicing group II introns, which are retrotransposons of bacterial origin. Our crystal structures at 3.4 and 3.5 angstrom of an excised group II intron in branched ("lariat") form show that the 2'-5' branch organizes a network of active-site tertiary interactions that position the intron terminal 3'-hydroxyl group into a configuration poised to initiate reverse splicing, the first step in retrotransposition. Moreover, the branchpoint and flanking helices must undergo a base-pairing switch after branch formation...
December 2, 2016: Science
https://www.readbyqxmd.com/read/27930312/metal-dependence-and-branched-rna-cocrystal-structures-of-the-rna-lariat-debranching-enzyme-dbr1
#10
Nathaniel E Clark, Adam Katolik, Kenneth M Roberts, Alexander B Taylor, Stephen P Holloway, Jonathan P Schuermann, Eric J Montemayor, Scott W Stevens, Paul F Fitzpatrick, Masad J Damha, P John Hart
Intron lariats are circular, branched RNAs (bRNAs) produced during pre-mRNA splicing. Their unusual chemical and topological properties arise from branch-point nucleotides harboring vicinal 2',5'- and 3',5'-phosphodiester linkages. The 2',5'-bonds must be hydrolyzed by the RNA debranching enzyme Dbr1 before spliced introns can be degraded or processed into small nucleolar RNA and microRNA derived from intronic RNA. Here, we measure the activity of Dbr1 from Entamoeba histolytica by using a synthetic, dark-quenched bRNA substrate that fluoresces upon hydrolysis...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27923990/regulation-of-prp43-mediated-disassembly-of-spliceosomes-by-its-cofactors-ntr1-and-ntr2
#11
Jean-Baptiste Fourmann, Marcel J Tauchert, Ralf Ficner, Patrizia Fabrizio, Reinhard Lührmann
The DEAH-box NTPase Prp43 disassembles spliceosomes in co-operation with the cofactors Ntr1/Spp382 and Ntr2, forming the NTR complex. How Prp43 is regulated by its cofactors to discard selectively only intron-lariat spliceosomes (ILS) and defective spliceosomes and to prevent disassembly of earlier and properly assembled/wild-type spliceosomes remains unclear. First, we show that Ntr1's G-patch motif (Ntr1GP) can be replaced by the GP motif of Pfa1/Sqs1, a Prp43's cofactor in ribosome biogenesis, demonstrating that the specific function of Ntr1GP is to activate Prp43 for spliceosome disassembly and not to guide Prp43 to its binding site in the spliceosome...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27898435/percutaneous-left-atrial-appendage-closure-current-state-of-the-art
#12
Mohammad-Ali Jazayeri, Venkat Vuddanda, Valay Parikh, Dhanunjaya R Lakkireddy
PURPOSE OF REVIEW: The authors reviewed the seminal and more recent literature surrounding the major modalities for percutaneous left atrial appendage closure used in contemporary practice, with particular emphasis on safety and efficacy, technical challenges, and future developments. RECENT FINDINGS: Along with the continued practice of surgical left atrial appendage closure, which has evolved substantially with the advent of clipping techniques, a number of percutaneous methods have been developed to close the left atrial appendage with endocardial, epicardial, and hybrid approaches...
January 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/27875300/the-fission-yeast-pre-mrna-processing-factor-18-prp18-has-intron-specific-splicing-functions-with-links-to-g1-s-cell-cycle-progression
#13
Nagampalli Vijaykrishna, Geetha Melangath, Rakesh Kumar, Piyush Khandelia, Pushpinder Bawa, Raghavan Varadarajan, Usha Vijayraghavan
The fission yeast genome, which contains numerous short introns, is an apt model for studies on fungal splicing mechanisms and splicing by intron definition. Here we perform a domain analysis of the evolutionarily conserved Schizosaccharomyces pombe pre-mRNA-processing factor, SpPrp18. Our mutational and biophysical analyses of the C-terminal α-helical bundle reveal critical roles for the conserved region as well as helix five. We generate a novel conditional missense mutant, spprp18-5 To assess the role of SpPrp18, we performed global splicing analyses on cells depleted of prp18(+) and the conditional spprp18-5 mutant, which show widespread but intron-specific defects...
December 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27870853/intron-lariat-rna-inhibits-microrna-biogenesis-by-sequestering-the-dicing-complex-in-arabidopsis
#14
Ziwei Li, Shengpeng Wang, Jinping Cheng, Chuanbin Su, Songxiao Zhong, Qi Liu, Yuda Fang, Yao Yu, Hong Lv, Yun Zheng, Binglian Zheng
Lariat RNAs formed as by-products of splicing are quickly degraded by the RNA debranching enzyme 1 (DBR1), leading to their turnover. Null dbr1 mutants in both animals and plants are embryo lethal, but the mechanism underlying the lethality remains unclear. Here we characterized a weak mutant allele of DBR1 in Arabidopsis, dbr1-2, and showed that a global increase in lariat RNAs was unexpectedly accompanied by a genome-wide reduction in miRNA accumulation. The dbr1-2 mutation had no effects on expression of miRNA biogenesis genes or primary miRNAs (pri-miRNAs), but the association of pri-miRNAs with the DCL1/HYL1 dicing complex was impaired...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27765821/mechanistic-insights-into-the-manganese-dependent-phosphodiesterase-activity-of-yeast-dbr1-with-bis-p-nitrophenylphosphate-and-branched-rna-substrates
#15
Beate Schwer, Fahad Khalid, Stewart Shuman
Saccharomyces cerevisiae Dbr1 is a manganese-dependent RNA debranching enzyme that cleaves the 2'-5' phosphodiester bond of the lariat introns formed during pre-mRNA splicing. Dbr1 is a member of the binuclear metallophosphoesterase enzyme superfamily. We showed previously via alanine scanning that RNA debranching in vivo and in vitro depends on conserved active site residues His13, Asp40, Asn85, His86, His179, His231, and His233. Here, by extending the alanine scan, we added Cys11 to the ensemble of essential active site components...
December 2016: RNA
https://www.readbyqxmd.com/read/27752134/the-b1-protein-guides-the-biosynthesis-of-a-lasso-peptide
#16
Shaozhou Zhu, Christopher D Fage, Julian D Hegemann, Andreas Mielcarek, Dushan Yan, Uwe Linne, Mohamed A Marahiel
Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) with a unique lariat knot-like fold that endows them with extraordinary stability and biologically relevant activity. However, the biosynthetic mechanism of these fascinating molecules remains largely speculative. Generally, two enzymes (B for processing and C for cyclization) are required to assemble the unusual knot-like structure. Several subsets of lasso peptide gene clusters feature a "split" B protein on separate open reading frames (B1 and B2), suggesting distinct functions for the B protein in lasso peptide biosynthesis...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27718444/conversion-of-persistent-atrial-fibrillation-to-sinus-rhythm-after-laa-ligation-with-the-lariat-device
#17
Nitish Badhwar, Suneet Mittal, Abdi Rasekh, Smit Vasaiwala, Dan Musat, Payam S Naeini, Qi Fang, Karin Nentwich, Thomas Deneke, Jie Chang, Dhanunjaya Lakkireddy, David Wilber, Randall J Lee
No abstract text is available yet for this article.
December 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27696317/left-atrial-appendage-closure-for-stroke-prevention-in-atrial-fibrillation
#18
REVIEW
Erin A Fender, Jawad G Kiani, David R Holmes
PURPOSE OF REVIEW: Anticoagulant therapy effectively reduces the incidence of stroke in patients with atrial fibrillation (AF) but is underutilized and frequently contraindicated. The left atrial appendage (LAA) is the primary site of thrombus formation in AF patients. Surgical and percutaneous appendage closure has been evaluated as a site-specific therapy to reduce systemic thromboembolism. RECENT FINDINGS: We will review LAA closure techniques, examine recent outcome data, and discuss the indications for, and potential complications of, each approach...
November 2016: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/27651124/percutaneous-left-atrial-appendage-occlusion-using-different-technologies-in-the-united-kingdom-a-multicenter-registry
#19
Timothy R Betts, Milena Leo, Sandeep Panikker, Prapa Kanagaratnam, Michael Koa-Wing, David Wyn Davies, David Hildick-Smith, Dylan G Wynne, Oliver Ormerod, Oliver R Segal, Anthony W Chow, Derick Todd, Sandra Cabrera Gomez, Graeme J Kirkwood, David Fox, Chris Pepper, John Foran, Tom Wong
OBJECTIVES: This study aimed at assessing the feasibility and long-term efficacy of left atrial appendage occlusion (LAAO) in a "real world" setting. BACKGROUND: Although LAAO has recently emerged as an alternative to oral anticoagulants in patients with atrial fibrillation for the prevention of thromboembolic stroke, "real world" data about the procedure with different devices are lacking. METHODS: Eight centers in the United Kingdom contributed to a retrospective registry for LAAO procedures undertaken between July 2009 and November 2014...
September 21, 2016: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/27637120/diagnosis-and-treatment-of-atrial-fibrillation
#20
Cecilia Gutierrez, Daniel G Blanchard
Atrial fibrillation is a supraventricular arrhythmia that adversely affects cardiac function and increases the risk of stroke. It is the most common arrhythmia and a major source of morbidity and mortality; its prevalence increases with age. Pulse rate is sensitive, but not specific, for diagnosis, and suspected atrial fibrillation should be confirmed with 12-lead electrocardiography. Because normal electrocardiographic findings do not rule out atrial fibrillation, home monitoring is recommended if there is clinical suspicion of arrhythmia despite normal test results...
September 15, 2016: American Family Physician
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