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https://www.readbyqxmd.com/read/28931690/conformational-changes-in-the-5-end-of-the-hiv-1-genome-dependent-on-the-debranching-enzyme-dbr1-during-early-stages-of-infection
#1
Alvaro E Galvis, Hugh E Fisher, Hung Fan, David Camerini
Previous studies in our laboratory showed that the RNA debranching enzyme (DBR1) is not required for early steps in HIV cDNA formation, but is necessary for synthesis of intermediate and late cDNA products. To further characterize this effect, we evaluated the topology of the 5' end of the HIV-1 RNA genome during early infection with and without inhibition of DBR1 synthesis. Cells were transfected with DBR1 shRNA followed 48 hours later by infection with an HIV-1 derived vector containing an RNase H deficient reverse transcriptase...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28919079/structure-of-an-intron-lariat-spliceosome-from-saccharomyces-cerevisiae
#2
Ruixue Wan, Chuangye Yan, Rui Bai, Jianlin Lei, Yigong Shi
The disassembly of the intron lariat spliceosome (ILS) marks the end of a splicing cycle. Here we report a cryoelectron microscopy structure of the ILS complex from Saccharomyces cerevisiae at an average resolution of 3.5 Å. The intron lariat remains bound in the spliceosome whereas the ligated exon is already dissociated. The step II splicing factors Prp17 and Prp18, along with Cwc21 and Cwc22 that stabilize the 5' exon binding to loop I of U5 small nuclear RNA (snRNA), have been released from the active site assembly...
September 8, 2017: Cell
https://www.readbyqxmd.com/read/28898453/echocardiographic-guidance-and-monitoring-of-left-atrial-appendage-closure-with-atriclip-during-open-chest-cardiac-surgery
#3
Rachele Contri, Sara Clivio, Tiziano Torre, Tiziano Cassina
Left atrial appendage (LAA) closure prevents thromboembolic risk and avoids lifelong anticoagulation due to atrial fibrillation (AF). Nowadays, AtriClip, a modern epicardial device approved in June 2010, allows external and safe closure of LAA in patients undergoing cardiac surgery during other open-chest cardiac surgical procedures. Such a surgical approach and its epicardial deployment differentiates LAA closure with AtriClip from percutaneous closure techniques such as Watchman (Boston Scientific, Marlborough, MA, USA), Lariat (SentreHEART Inc...
September 12, 2017: Echocardiography
https://www.readbyqxmd.com/read/28733144/the-spliceosome-a-protein-directed-metalloribozyme
#4
REVIEW
Yigong Shi
Pre-mRNA splicing is executed by the ribonucleoprotein machinery spliceosome. Nearly 40 years after the discovery of pre-mRNA splicing, the atomic structure of the spliceosome has finally come to light. Four distinct conformational states of the yeast spliceosome have been captured at atomic or near-atomic resolutions. Two catalytic metal ions at the active site are specifically coordinated by the U6 small nuclear RNA (snRNA) and catalyze both the branching reaction and the exon ligation. Of the three snRNAs in the fully assembled spliceosome, U5 and U6, along with 30 contiguous nucleotides of U2 at its 5'-end, remain structurally rigid throughout the splicing reaction...
August 18, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28648679/structure-determination-of-group-ii-introns
#5
REVIEW
Timothy Wiryaman, Navtej Toor
Group II introns are self-splicing catalytic RNAs that are able to excise themselves from pre-mRNAs using a mechanism identical to that utilized by the spliceosome. Both structural and phylogenetic data support the hypothesis that group II introns and the spliceosome share a common ancestor. Structures of group II introns have given insight into the active site required for the catalysis of RNA splicing. This review outlines crucial aspects of the structure determination of group II introns such as sample preparation and data processing...
August 1, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28639873/anesthetic-management-of-patients-undergoing-percutaneous-endocardial-and-epicardial-left-atrial-appendage-occlusion
#6
Zeena Husain, Payam Safavi-Naeini, Abdi Rasekh, Mehdi Razavi, Charles D Collard, James M Anton, Daniel A Tolpin
Atrial fibrillation is the most common cardiac arrhythmia in adults affecting almost 6 million adults in the United States. The 2 most common comorbidities associated with atrial fibrillation are heart failure and thromboembolic events. Heart failure symptoms may be treated with rate control, antiarrhythmic medications or by catheter ablation. Unfortunately, despite optimal medical management, thromboembolic events still occur. Recently, there has been a great deal of interest and innovation in finding an alternative to chronic anticoagulation...
June 1, 2017: Seminars in Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28634583/circular-rnas-biogenesis-function-and-role-in-human-diseases
#7
REVIEW
John Greene, Anne-Marie Baird, Lauren Brady, Marvin Lim, Steven G Gray, Raymond McDermott, Stephen P Finn
Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28624615/cell-size-dependent-transcription-of-flc-and-its-antisense-long-non-coding-rna-coolair-explain-cell-to-cell-expression-variation
#8
Robert Ietswaart, Stefanie Rosa, Zhe Wu, Caroline Dean, Martin Howard
Single-cell quantification of transcription kinetics and variability promotes a mechanistic understanding of gene regulation. Here, using single-molecule RNA fluorescence in situ hybridization and mathematical modeling, we dissect cellular RNA dynamics for Arabidopsis FLOWERING LOCUS C (FLC). FLC expression quantitatively determines flowering time and is regulated by antisense (COOLAIR) transcription. In cells without observable COOLAIR expression, we quantify FLC transcription initiation, elongation, intron processing, and lariat degradation, as well as mRNA release from the locus and degradation...
June 28, 2017: Cell Systems
https://www.readbyqxmd.com/read/28621679/circular-rnas-a-novel-type-of-biomarker-and-genetic-tools-in-cancer
#9
REVIEW
Yi-Neng Han, Sheng-Qiang Xia, Yuan-Yuan Zhang, Jun-Hua Zheng, Wei Li
Circular RNAs (circRNAs) are a novel type of universal and diverse endogenous noncoding RNAs (ncRNAs) and they form a covalently closed continuous loop without 5' or 3' tails unlike linear RNAs. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific expression. CircRNAs are generated either from exons or introns by back splicing or lariat introns. CircRNAs play important roles as miRNA sponges, gene transcription and expression regulators, RNA-binding protein (RBP) sponges and protein/peptide translators...
June 2, 2017: Oncotarget
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
#10
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...
July 2017: FEBS Letters
https://www.readbyqxmd.com/read/28502770/an-atomic-structure-of-the-human-spliceosome
#11
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
#12
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
#13
REVIEW
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...
June 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28457791/left-atrial-appendage-occlusion-for-stroke-prevention
#14
REVIEW
Arijit Chanda, John P Reilly
More than 2.3 million 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...
May 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
#15
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
#16
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...
June 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
#17
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
#18
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
#19
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
#20
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
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