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https://www.readbyqxmd.com/read/27923990/regulation-of-prp43-mediated-disassembly-of-spliceosomes-by-its-cofactors-ntr1-and-ntr2
#1
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
#2
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
#3
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 alpha-helical bundle reveal critical roles for the conserved region as well as and 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...
November 15, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27870853/intron-lariat-rna-inhibits-microrna-biogenesis-by-sequestering-the-dicing-complex-in-arabidopsis
#4
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
#5
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
#6
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
#7
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.
September 28, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27696317/left-atrial-appendage-closure-for-stroke-prevention-in-atrial-fibrillation
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27611791/structure-and-mechanism-of-the-sphingopyxin%C3%A2-i-lasso-peptide-isopeptidase
#11
Christopher D Fage, Julian D Hegemann, Annika J Nebel, Roman M Steinbach, Shaozhou Zhu, Uwe Linne, Klaus Harms, Gert Bange, Mohamed A Marahiel
Lasso peptides are natural products that assume a unique lariat knot topology. Lasso peptide isopeptidases (IsoPs) eliminate this topology through isopeptide bond cleavage. To probe how these enzymes distinguish between substrates and hydrolyze only isopeptide bonds, we examined the structure and mechanism of a previously uncharacterized IsoP from the proteobacterium Sphingopyxis alaskensis RB2256 (SpI-IsoP). We demonstrate that SpI-IsoP efficiently and specifically linearizes the lasso peptide sphingopyxin I (SpI) and variants thereof...
October 4, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27611563/antibiotic-potency-against-e-%C3%A2-coli-is-enhanced-by-channel-forming-alkyl-lariat-ethers
#12
Saeedeh Negin, Mohit B Patel, Michael R Gokel, Joseph W Meisel, George W Gokel
Several N,N'-bis(n-alkyl-4,13-diaza[18]crown-6) lariat ethers were found to significantly enhance the potency of rifampicin and tetracycline, but not erythromycin and kanamycin, against the non-pathogenic DH5α and K-12 strains of Escherichia coli when administered at levels below their minimum inhibitory concentrations (MICs). The enhancements in antibiotic potency observed for the lariat ethers ranged from three- to 20-fold, depending on the strain of E. coli, the antibiotic, and the lengths of the alkyl chains attached at the macroring nitrogen atoms...
September 9, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27566151/alternative-splicing-of-u2af1-reveals-a-shared-repression-mechanism-for-duplicated-exons
#13
Jana Kralovicova, Igor Vorechovsky
The auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF) facilitates branch point (BP) recognition and formation of lariat introns. The gene for the 35-kD subunit of U2AF gives rise to two protein isoforms (termed U2AF35a and U2AF35b) that are encoded by alternatively spliced exons 3 and Ab, respectively. The splicing recognition sequences of exon 3 are less favorable than exon Ab, yet U2AF35a expression is higher than U2AF35b across tissues. We show that U2AF35b repression is facilitated by weak, closely spaced BPs next to a long polypyrimidine tract of exon Ab...
August 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27473169/identification-of-new-branch-points-and-unconventional-introns-in-saccharomyces-cerevisiae
#14
Genevieve M Gould, Joseph M Paggi, Yuchun Guo, David V Phizicky, Boris Zinshteyn, Eric T Wang, Wendy V Gilbert, David K Gifford, Christopher B Burge
Spliced messages constitute one-fourth of expressed mRNAs in the yeast Saccharomyces cerevisiae, and most mRNAs in metazoans. Splicing requires 5' splice site (5'SS), branch point (BP), and 3' splice site (3'SS) elements, but the role of the BP in splicing control is poorly understood because BP identification remains difficult. We developed a high-throughput method, Branch-seq, to map BPs and 5'SSs of isolated RNA lariats. Applied to S. cerevisiae, Branch-seq detected 76% of expressed, annotated BPs and identified a comparable number of novel BPs...
October 2016: RNA
https://www.readbyqxmd.com/read/27459055/cryo-em-structure-of-the-spliceosome-immediately-after-branching
#15
Wojciech P Galej, Max E Wilkinson, Sebastian M Fica, Chris Oubridge, Andrew J Newman, Kiyoshi Nagai
Pre-mRNA splicing proceeds by two consecutive trans-esterification reactions via a lariat-intron intermediate. We present the 3.8 Å cryo-EM structure of the spliceosome immediately after lariat formation. The 5'-splice site is cleaved but remains close to the catalytic Mg(2+) site in the U2/U6 snRNA triplex, and the 5'-phosphate of the intron nucleotide G(+1) is linked to the branch adenosine 2'OH. The 5'-exon is held between the Prp8 amino-terminal and Linker domains, and base-pairs with U5 snRNA loop 1...
July 26, 2016: Nature
https://www.readbyqxmd.com/read/27457620/structure-activity-analysis-of-gram-positive-bacterium-producing-lasso-peptides-with-anti-mycobacterial-activity
#16
Junji Inokoshi, Nobuhiro Koyama, Midori Miyake, Yuji Shimizu, Hiroshi Tomoda
Lariatin A, an 18-residue lasso peptide encoded by the five-gene cluster larABCDE, displays potent and selective anti-mycobacterial activity. The structural feature is an N-terminal macrolactam ring, through which the C-terminal passed to form the rigid lariat-protoknot structure. In the present study, we established a convergent expression system by the strategy in which larA mutant gene-carrying plasmids were transformed into larA-deficient Rhodococcus jostii, and generated 36 lariatin variants of the precursor protein LarA to investigate the biosynthesis and the structure-activity relationships...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27445308/structure-of-a-yeast-catalytic-step-i-spliceosome-at-3-4-%C3%A3-resolution
#17
Ruixue Wan, Chuangye Yan, Rui Bai, Gaoxingyu Huang, Yigong Shi
Each cycle of pre-messenger RNA splicing, carried out by the spliceosome, comprises two sequential transesterification reactions, which result in the removal of an intron and the joining of two exons. Here we report an atomic structure of a catalytic step I spliceosome (known as the C complex) from Saccharomyces cerevisiae, as determined by cryo-electron microscopy at an average resolution of 3.4 angstroms. In the structure, the 2'-OH of the invariant adenine nucleotide in the branch point sequence (BPS) is covalently joined to the phosphate at the 5' end of the 5' splice site (5'SS), forming an intron lariat...
August 26, 2016: Science
https://www.readbyqxmd.com/read/27198687/clinical-significance-of-leaks-following-left-atrial-appendage-ligation-with-the%C3%A2-lariat-suture-delivery-device
#18
EDITORIAL
Randall J Lee
No abstract text is available yet for this article.
May 23, 2016: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/27198686/clinical-implications-of-leaks-following-left-atrial-appendage-ligation-with%C3%A2-the%C3%A2-lariat-device
#19
Carola Gianni, Luigi Di Biase, Chintan Trivedi, Sanghamitra Mohanty, Yalçın Gökoğlan, Mahmut F Güneş, Rong Bai, Amin Al-Ahmad, J David Burkhardt, Rodney P Horton, Andrew K Krumerman, Eugen C Palma, Miguel Valderrábano, Douglas Gibson, Matthew J Price, Andrea Natale
OBJECTIVES: The aim of this study was to evaluate the incidence and clinical implications of leaks (acute incomplete occlusion, early and late reopenings) following LAA ligation with the LARIAT device. BACKGROUND: Percutaneous LAA ligation with the LARIAT device may represent an alternative for stroke prevention in high-risk patients with atrial fibrillation with contraindications to oral anticoagulation. METHODS: This was a retrospective, multicenter study of 98 consecutive patients undergoing successful LAA ligation with the LARIAT device...
May 23, 2016: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/27128539/left-atrial-appendage-ligation-with-the-next-generation-lariat-suture-delivery-device-early-clinical-experience
#20
Krzysztof Bartus, Sameer Gafoor, David Tschopp, John P Foran, Roland Tilz, Tom Wong, Dhanunjaya Lakkireddy, Horst Sievert, Randall J Lee
BACKGROUND: The purpose of the study was to determine the efficacy and safety of left atrial appendage (LAA) closure with a micropuncture pericardial access approach and the new LARIAT(+) suture delivery device. METHODS: Seventy-two patients with atrial fibrillation were enrolled to undergo telescopic micropuncture pericardial access and percutaneous ligation of the LAA with the LARIAT(+) device. LAA closure was confirmed with transesophageal echocardiography (TEE) and contrast fluoroscopy immediately, then with TEE at 30days and 90days post-LAA ligation...
July 15, 2016: International Journal of Cardiology
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