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https://www.readbyqxmd.com/read/28504306/crystal-structure-of-the-entamoeba-histolytica-rna-lariat-debranching-enzyme-ehdbr1-reveals-a-catalytic-zn-2-mn-2-heterobinucleation
#1
Elizabeth Ransey, Eduardo Paredes, Sourav K Dey, Subha R Das, Annie Heroux, Mark R Macbeth
The RNA lariat debranching enzyme Dbr1 is a metallophosphoesterase that cleaves 2'-5' phosphodiester bonds within intronic lariats. Previous reports have indicated that Dbr1 enzymatic activity is supported by diverse metal ions including Ni(2+) , Mn(2+) , Mg(2+) , Fe(2+) and Zn(2+) . While in initial structures of the Entamoeba histolytica Dbr1 only one of the two catalytic metal-binding sites were observed to be occupied (with a Mn(2+) ion), recent structures determined a Zn(2+) /Fe(2+) heterobinucleation...
May 15, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28502770/an-atomic-structure-of-the-human-spliceosome
#2
Xiaofeng Zhang, Chuangye Yan, Jing Hang, Lorenzo I Finci, Jianlin Lei, Yigong Shi
Mechanistic understanding of pre-mRNA splicing requires detailed structural information on various states of the spliceosome. Here we report the cryo electron microscopy (cryo-EM) structure of the human spliceosome just before exon ligation (the C(∗) complex) at an average resolution of 3.76 Å. The splicing factor Prp17 stabilizes the active site conformation. The step II factor Slu7 adopts an extended conformation, binds Prp8 and Cwc22, and is poised for selection of the 3'-splice site. Remarkably, the intron lariat traverses through a positively charged central channel of RBM22; this unusual organization suggests mechanisms of intron recruitment, confinement, and release...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28495309/group-ii-introns-in-wheat-mitochondria-have-degenerate-structural-features-and-varied-splicing-pathways
#3
Matthew Ngu, Karen Massel, Linda Bonen
Mitochondrial introns in flowering plant genes are virtually all classified as members of the group II ribozyme family although certain structural features have degenerated to varying degrees over evolutionary time. We are interested in the impact that unconventional intron architecture might have on splicing biochemistry in vivo and we have focused in particular on intronic domains V and VI, which for self-splicing introns provide a key component of the catalytic core and the bulged branchpoint adenosine, respectively...
May 8, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28485684/circular-rna-new-member-of-noncoding-rna-with-novel-functions
#4
Kuei-Yang Hsiao, H Sunny Sun, Shaw-Jenq Tsai
A growing body of evidence indicates that circular RNAs are not simply a side product of splicing but a new class of noncoding RNAs in higher eukaryotes. The progression for the studies of circular RNAs is accelerated by combination of several advanced technologies such as next generation sequencing, gene silencing (small interfering RNAs) and editing (CRISPR/Cas9). More and more studies showed that dysregulated expression of circular RNAs plays critical roles during the development of several human diseases...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28457791/left-atrial-appendage-occlusion-for-stroke-prevention
#5
Arijit Chanda, John P Reilly
More than 2.3 millions adults in the United States have atrial fibrillation (AF), which exposes them to a 5- fold increased risk of stroke. The left atrial appendage (LAA) appears to be the source of thrombus formation in the vast majority of these patients. Anticoagulation significantly reduces the risk of stroke, but often we encounter patients who have absolute or relative contraindication to anticoagulation. Percutaneous LAA exclusion offers an alternative to anticoagulation to decrease the risk of stroke...
April 27, 2017: Progress in Cardiovascular Diseases
https://www.readbyqxmd.com/read/28456775/atrial-natriuretic-peptide-and-brain-natriuretic-peptide-changes-after-epicardial-percutaneous-left-atrial-appendage-suture-ligation-using-lariat-device
#6
K Bartus, J Podolec, R J Lee, B Kapelak, J Sadowski, M Bartus, K Oles, P Ceranowicz, R Trabka, R Litwinowicz
Percutaneous left atrial appendage closure is an alternative treatment for stroke and systemic thromboembolism risk reduction in non-valvular atrial fibrillation (AF). However, the neurohormonal impact of epicardial exclusion of the left atrial appendage (LAA) with the LARIAT procedure is unknown. Evaluation of changes in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in AF patients underwent percutaneous LAA suture ligation. Sixty six patients underwent successfully percutaneous LAA suture ligation using LARIAT device...
February 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28438387/structural-insights-into-the-mechanism-of-group-ii-intron-splicing
#7
REVIEW
Chen Zhao, Anna Marie Pyle
While the major architectural features and active-site components of group II introns have been known for almost a decade, information on the individual stages of splicing has been lacking. Recent advances in crystallography and cryo-electron microscopy (cryo-EM) have provided major new insights into the structure of intact lariat introns. Conformational changes that mediate the steps of splicing and retrotransposition are being elucidated, revealing the dynamic, highly coordinated motions that are required for group II intron activity...
April 21, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28429401/synthesis-of-l-threitol-based-crown-ethers-and-their-application-as-enantioselective-phase-transfer-catalyst-in-michael-additions
#8
Zsolt Rapi, Tamás Nemcsok, Ádám Pálvölgyi, György Keglevich, Alajos Grün, Péter Bakó
A few new l-threitol-based lariat ethers incorporating a monoaza-15-crown-5 unit were synthesized starting from diethyl l-tartrate. These macrocycles were used as phase transfer catalysts in asymmetric Michael addition reactions under mild conditions to afford the adducts in a few cases in good to excellent enantioselectivities. The addition of 2-nitropropane to trans-chalcone, and the reaction of diethyl acetamidomalonate with β-nitrostyrene resulted in the chiral Michael adducts in good enantioselectivities (90% and 95%, respectively)...
June 2017: Chirality
https://www.readbyqxmd.com/read/28421220/a-highly-selective-colorimetric-and-environment-sensitive-optical-potassium-ion-sensor
#9
Guangjie Song, Ruofan Sun, Jiqing Du, Meiwan Chen, Yanqing Tian
Potassium ions (K(+)) play vital roles in many biological processes and thus highly selective sensors for K(+) are critical for disease diagnosis and health monitoring. Herein, we report a colorimetric K(+) sensor (KS7) in which a hemicyanine dye was used as a fluorophore and phenylaza-[18]crown-6 lariat ether (ACLE) was utilized as a K(+) ligand. The maximum absorption peak of KS7 shifted hypsochromically by 77 nm (from 515 to 438 nm) with an isosbestic point at 452 nm upon the addition of K(+) to its aqueous solution accompanied by a color change from red to yellow...
April 19, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28416677/structural-toggle-in-the-rnaseh-domain-of-prp8-helps-balance-splicing-fidelity-and-catalytic-efficiency
#10
Megan Mayerle, Madhura Raghavan, Sarah Ledoux, Argenta Price, Nicholas Stepankiw, Haralambos Hadjivassiliou, Erica A Moehle, Senén D Mendoza, Jeffrey A Pleiss, Christine Guthrie, John Abelson
Pre-mRNA splicing is an essential step of eukaryotic gene expression that requires both high efficiency and high fidelity. Prp8 has long been considered the "master regulator" of the spliceosome, the molecular machine that executes pre-mRNA splicing. Cross-linking and structural studies place the RNaseH domain (RH) of Prp8 near the spliceosome's catalytic core and demonstrate that prp8 alleles that map to a 17-aa extension in RH stabilize it in one of two mutually exclusive structures, the biological relevance of which are unknown...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28368002/macrocycle-peptides-delineate-locked-open-inhibition-mechanism-for-microorganism-phosphoglycerate-mutases
#11
Hao Yu, Patricia Dranchak, Zhiru Li, Ryan MacArthur, Matthew S Munson, Nurjahan Mehzabeen, Nathan J Baird, Kevin P Battalie, David Ross, Scott Lovell, Clotilde K S Carlow, Hiroaki Suga, James Inglese
Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode iPGM to select and enrich lariat-like ligands from an mRNA-display macrocyclic peptide library containing >10(12) members...
April 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28262556/rapid-discovery-of-potent-and-selective-glycosidase-inhibiting-de-novo-peptides
#12
Seino A K Jongkees, Sami Caner, Christina Tysoe, Gary D Brayer, Stephen G Withers, Hiroaki Suga
Human pancreatic α-amylase (HPA) is responsible for degrading starch to malto-oligosaccharides, thence to glucose, and is therefore an attractive therapeutic target for the treatment of diabetes and obesity. Here we report the discovery of a unique lariat nonapeptide, by means of the RaPID (Random non-standard Peptides Integrated Discovery) system, composed of five amino acids in a head-to-side-chain thioether macrocycle and a further four amino acids in a 310 helical C terminus. This is a potent inhibitor of HPA (Ki = 7 nM) yet exhibits selectivity for the target over other glycosidases tested...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28185365/circular-rnas-biogenesis-properties-roles-and-their-relationships-with-liver-diseases
#13
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 a 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 by way of extracellular vesicles. They have some advantages such as stability, conservation, and tissue specificity. By serving as sponges of microRNAs, interacting with long non-coding RNAs, mRNA, or proteins, circRNAs regulate gene expression at transcriptional and post-transcriptional levels and contribute to carcinogenesis...
May 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28159804/lariat-capping-as-a-tool-to-manipulate-the-5-end-of-individual-yeast-mrna-species-in-vivo
#14
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 analyze 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 m(7)G 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...
May 2017: RNA
https://www.readbyqxmd.com/read/28119336/large-scale-analysis-of-branchpoint-usage-across-species-and-cell-lines
#15
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 11 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...
April 2017: Genome Research
https://www.readbyqxmd.com/read/28076345/structure-of-a-spliceosome-remodelled-for-exon-ligation
#16
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
#17
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
#18
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)...
May 5, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27980089/structure-of-a-yeast-step-ii-catalytically-activated-spliceosome
#19
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
#20
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
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