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https://www.readbyqxmd.com/read/28650401/progressive-brain-atrophy-despite-persistent-viral-suppression-in-hiv-over-age-60
#1
Katherine M Clifford, Vishal Samboju, Yann Cobigo, Benedetta Milanini, Gabriel A Marx, Joanna M Hellmuth, Howard J Rosen, Joel H Kramer, Isabel E Allen, Victor G Valcour
BACKGROUND: Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared to that of healthy aging. METHODS: We examined longitudinal structural brain MRI atrophy rates employing region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants over age 60 years (n=38) compared to age-matched HIV-uninfected healthy and cognitively normal controls (n=24)...
June 22, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28650318/tandem-hnrnp-a1-rna-recognition-motifs-act-in-concert-to-repress-the-splicing-of-survival-motor-neuron-exon-7
#2
Irene Beusch, Pierre Barraud, Ahmed Moursy, Antoine Cléry, Frédéric Hai-Trieu Allain
HnRNP A1 regulates many alternative splicing events by the recognition of splicing silencer elements. Here, we provide the solution structures of its two RNA recognition motifs (RRMs) in complex with short RNA. In addition, we show by NMR that both RRMs of hnRNP A1 can bind simultaneously to a single bipartite motif of the human intronic splicing silencer ISS-N1, which controls survival of motor neuron exon 7 splicing. RRM2 binds to the upstream motif and RRM1 to the downstream motif. Combining the insights from the structure with in cell splicing assays we show that the architecture and organization of the two RRMs is essential to hnRNP A1 function...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28650145/the-dead-box-protein-cyt-19-uses-arginine-residues-in-its-c-tail-to-tether-rna-substrates
#3
Veronica F Busa, Maxwell J Rector, Rick Russell
DEAD-box proteins are nonprocessive RNA helicases that play diverse roles in cellular processes. The Neurospora crassa DEAD-box protein CYT-19 promotes mitochondrial group I intron splicing and functions as a general RNA chaperone. CYT-19 includes a disordered, arginine-rich 'C-tail' that binds RNA, positioning the helicase core to capture and unwind nearby RNA helices. Here we probed the C-tail further by varying the number and positions of arginines within it. We found that removing sets of as few as four of the eleven arginines reduced RNA unwinding activity (kcat/KM) equivalently to removing the C-tail, suggesting that a minimum or 'threshold' number of arginines is required...
June 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28649985/attenuation-of-rna-polymerase-ii-pausing-mitigates-brca1-associated-r-loop-accumulation-and-tumorigenesis
#4
Xiaowen Zhang, Huai-Chin Chiang, Yao Wang, Chi Zhang, Sabrina Smith, Xiayan Zhao, Sreejith J Nair, Joel Michalek, Ismail Jatoi, Meeghan Lautner, Boyce Oliver, Howard Wang, Anna Petit, Teresa Soler, Joan Brunet, Francesca Mateo, Miguel Angel Pujana, Elizabeth Poggi, Krysta Chaldekas, Claudine Isaacs, Beth N Peshkin, Oscar Ochoa, Frederic Chedin, Constantine Theoharis, Lu-Zhe Sun, Tyler J Curiel, Richard Elledge, Victor X Jin, Yanfen Hu, Rong Li
Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28649982/structural-and-regulatory-diversity-shape-hla-c-protein-expression-levels
#5
Gurman Kaur, Stephanie Gras, Jesse I Mobbs, Julian P Vivian, Adrian Cortes, Thomas Barber, Subita Balaram Kuttikkatte, Lise Torp Jensen, Kathrine E Attfield, Calliope A Dendrou, Mary Carrington, Gil McVean, Anthony W Purcell, Jamie Rossjohn, Lars Fugger
Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28649752/investigating-dna-rna-and-protein-based-features-as-a-means-to-discriminate-pathogenic-synonymous-variants
#6
Mark Livingstone, Lukas Folkman, Yuedong Yang, Ping Zhang, Matthew Mort, David N Cooper, Yunlong Liu, Bela Stantic, Yaoqi Zhou
Synonymous single nucleotide variants (SNVs), although they do not alter the encoded protein sequences, have been implicated in many genetic diseases. Experimental studies indicate that synonymous SNVs can lead to changes in the secondary and tertiary structures of DNA and RNA, thereby impacting translational efficiency, co-translational protein folding as well as the binding of DNA/RNA-binding proteins. However, the importance of these various features in disease phenotypes is not clearly understood. Here we have built a support vector machine model (termed DDIG-SN) as a means to discriminate disease-causing synonymous variants...
June 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/28648754/what-can-human-guided-simulations-bring-to-rna-folding
#7
Liuba Mazzanti, Sébastien Doutreligne, Cedric Gageat, Philippe Derreumaux, Antoine Taly, Marc Baaden, Samuela Pasquali
Inspired by the recent success of scientific-discovery games for predicting protein tertiary and RNA secondary structures, we have developed an open software for coarse-grained RNA folding simulations, guided by human intuition. To determine the extent to which interactive simulations can accurately predict 3D RNA structures of increasing complexity and lengths (four RNAs with 22-47 nucleotides), an interactive experiment was conducted with 141 participants who had very little knowledge of nucleic acids systems and computer simulations, and had received only a brief description of the important forces stabilizing RNA structures...
June 22, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28648680/reversibly-constraining-spliceosome-substrate-complexes-by-engineering-disulfide-crosslinks
#8
Patrick McCarthy, Erin Garside, Yonatan Meschede-Krasa, Andrew MacMillan, Daniel Pomeranz Krummel
The spliceosome is a highly dynamic mega-Dalton enzyme, formed in part by assembly of U snRNPs onto its pre-mRNA substrate transcripts. Early steps in spliceosome assembly are challenging to study biochemically and structurally due to compositional and conformational dynamics. We detail an approach to covalently and reversibly constrain or trap non-covalent pre-mRNA/protein spliceosome complexes. This approach involves engineering a single disulfide bond between a thiol-bearing cysteine sidechain and a proximal backbone phosphate of the pre-mRNA, site-specifically modified with an N-thioalkyl moiety...
June 22, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28648679/structure-determination-of-group-ii-introns
#9
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...
June 22, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28648606/the-structure-of-the-r2tp-complex-defines-a-platform-for-recruiting-diverse-client-proteins-to-the-hsp90-molecular-chaperone-system
#10
Angel Rivera-Calzada, Mohinder Pal, Hugo Muñoz-Hernández, Juan R Luque-Ortega, David Gil-Carton, Gianluca Degliesposti, J Mark Skehel, Chrisostomos Prodromou, Laurence H Pearl, Oscar Llorca
The R2TP complex, comprising the Rvb1p-Rvb2p AAA-ATPases, Tah1p, and Pih1p in yeast, is a specialized Hsp90 co-chaperone required for the assembly and maturation of multi-subunit complexes. These include the small nucleolar ribonucleoproteins, RNA polymerase II, and complexes containing phosphatidylinositol-3-kinase-like kinases. The structure and stoichiometry of yeast R2TP and how it couples to Hsp90 are currently unknown. Here, we determine the 3D organization of yeast R2TP using sedimentation velocity analysis and cryo-electron microscopy...
June 6, 2017: Structure
https://www.readbyqxmd.com/read/28646195/structural-alteration-of-a-bydv-like-translation-element-bte-that-attenuates-p35-expression-in-three-mild-tobacco-bushy-top-virus-isolates
#11
Deya Wang, Chengming Yu, Shanshan Liu, Guolu Wang, Kerong Shi, Xiangdong Li, Xuefeng Yuan
To identify the molecular effects of Tobacco bushy top virus (TBTV) evolution on the degeneration of tobacco bushy top disease, three TBTV isolates with mild virulence were compared with wild-type TBTV to assess the translation of p35, which relies on a BYDV-like translation element (BTE) in a cap-independent manner. The in vitro expression of p35 in the mild isolates was only 20% to 40% of the expression observed in wt TBTV. Based on translation data from chimeric TBTV RNA, low-level p35 expression in the three mild isolates was associated with two regions: the 5' terminal 500 nt region (RI) and the 3' internal region (RV), which included the BTE...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646134/complete-mitochondrial-genome-of-clistocoeloma-sinensis-brachyura-grapsoidea-gene-rearrangements-and-higher-level-phylogeny-of-the-brachyura
#12
Zhao-Zhe Xin, Yu Liu, Dai-Zhen Zhang, Xin-Yue Chai, Zheng-Fei Wang, Hua-Bin Zhang, Chun-Lin Zhou, Bo-Ping Tang, Qiu-Ning Liu
Deciphering the animal mitochondrial genome (mitogenome) is very important to understand their molecular evolution and phylogenetic relationships. In this study, the complete mitogenome of Clistocoeloma sinensis was determined. The mitogenome of C. sinensis was 15,706 bp long, and its A+T content was 75.7%. The A+T skew of the mitogenome of C. sinensis was slightly negative (-0.020). All the transfer RNA genes had the typical cloverleaf structure, except for the trnS1 gene, which lacked a dihydroxyuridine arm...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645916/structures-and-dynamics-of-hibernating-ribosomes-from-staphylococcus-aureus-mediated-by-intermolecular-interactions-of-hpf
#13
Iskander Khusainov, Quentin Vicens, Rustam Ayupov, Konstantin Usachev, Alexander Myasnikov, Angelita Simonetti, Shamil Validov, Bruno Kieffer, Gulnara Yusupova, Marat Yusupov, Yaser Hashem
In bacteria, ribosomal hibernation shuts down translation as a response to stress, through reversible binding of stress-induced proteins to ribosomes. This process typically involves the formation of 100S ribosome dimers. Here, we present the structures of hibernating ribosomes from human pathogen Staphylococcus aureus containing a long variant of the hibernation-promoting factor (SaHPF) that we solved using cryo-electron microscopy. Our reconstructions reveal that the N-terminal domain (NTD) of SaHPF binds to the 30S subunit as observed for shorter variants of HPF in other species...
June 23, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28645155/features-of-genomic-organization-in-a-nucleotide-resolution-molecular-model-of-the-escherichia-coli-chromosome
#14
William C Hacker, Shuxiang Li, Adrian H Elcock
We describe structural models of the Escherichia coli chromosome in which the positions of all 4.6 million nucleotides of each DNA strand are resolved. Models consistent with two basic chromosomal orientations, differing in their positioning of the origin of replication, have been constructed. In both types of model, the chromosome is partitioned into plectoneme-abundant and plectoneme-free regions, with plectoneme lengths and branching patterns matching experimental distributions, and with spatial distributions of highly-transcribed chromosomal regions matching recent experimental measurements of the distribution of RNA polymerases...
June 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28645153/defective-mitochondrial-rna-processing-due-to-pnpt1-variants-causes-leigh-syndrome
#15
Sanna Matilainen, Christopher J Carroll, Uwe Richter, Liliya Euro, Max Pohjanpelto, Anders Paetau, Pirjo Isohanni, Anu Suomalainen
Leigh syndrome is a severe infantile encephalopathy with an exceptionally variable genetic background. We studied the exome of a child manifesting with Leigh syndrome at one month of age and progressing to death by the age of 2.4 years, and identified novel compound heterozygous variants in PNPT1, encoding the polynucleotide phosphorylase (PNPase). Expression of the wild type PNPT1 in the subject's myoblasts functionally complemented the defects, and the pathogenicity was further supported by structural predictions and protein and RNA analyses...
June 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28645111/intersecting-transcriptomic-profiling-technologies-and-long-non-coding-rna-function-in-lung-adenocarcinoma-discovery-mechanisms-and-therapeutic-applications
#16
REVIEW
Jonathan Castillo, Theresa R Stueve, Crystal N Marconett
Previously thought of as junk transcripts and pseudogene remnants, long non-coding RNAs (lncRNAs) have come into their own over the last decade as an essential component of cellular activity, regulating a plethora of functions within multicellular organisms. lncRNAs are now known to participate in development, cellular homeostasis, immunological processes, and the development of disease. With the advent of next generation sequencing technology, hundreds of thousands of lncRNAs have been identified. However, movement beyond mere discovery to the understanding of molecular processes has been stymied by the complicated genomic structure, tissue-restricted expression, and diverse regulatory roles lncRNAs play...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644867/host-derived-apolipoproteins-play-comparable-roles-with-viral-secretory-proteins-erns-and-ns1-in-the-infectious-particle-formation-of-flaviviridae
#17
Takasuke Fukuhara, Tomokazu Tamura, Chikako Ono, Mai Shiokawa, Hiroyuki Mori, Kentaro Uemura, Satomi Yamamoto, Takeshi Kurihara, Toru Okamoto, Ryosuke Suzuki, Kentaro Yoshii, Takeshi Kurosu, Manabu Igarashi, Hiroshi Aoki, Yoshihiro Sakoda, Yoshiharu Matsuura
Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV) particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein Erns or a non-structural protein 1 (NS1) as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of Erns are important for anchoring to viral membrane...
June 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28643555/unexpected-detection-of-porcine-rotavirus-c-strains-carrying-human-origin-vp6-gene
#18
Jobin Jose Kattoor, Sharad Saurabh, Yashpal Singh Malik, Shubhankar Sircar, Kuldeep Dhama, Souvik Ghosh, Krisztián Bányai, Nobumichi Kobayashi, Raj Kumar Singh
BACKGROUND: Rotavirus C (RVC), a known etiological agent of diarrheal outbreaks, mainly inflicts swine population globally with sporadic incidence in human, cattle, ferret, mink and dog. OBJECTIVE: To demonstrate presence of RVC in Indian swine population and characterisation of its selected structural (VP6) and non-structural (NSP4 and NSP5) genes. METHODS: A total of 108 diarrheic samples from different regions of India were used. Isolated RNA was loaded onto polyacrylamide gel to screen for the presence of RVs through the identification of specific electrophoretic genomic migration pattern...
June 23, 2017: Veterinary Quarterly
https://www.readbyqxmd.com/read/28643180/first-complete-genome-sequences-of-genogroup-v-genotype-3-porcine-sapoviruses-common-5-terminal-genomic-feature-of-sapoviruses
#19
Tomoichiro Oka, Yen Hai Doan, Takashi Shimoike, Kei Haga, Takenori Takizawa
Sapoviruses (SaVs) are enteric viruses and have been detected in various mammals. They are divided into multiple genogroups and genotypes based on the entire major capsid protein (VP1) encoding region sequences. In this study, we determined the first complete genome sequences of two genogroup V, genotype 3 (GV.3) SaV strains detected from swine fecal samples, in combination with Illumina MiSeq sequencing of the libraries prepared from viral RNA and PCR products. The lengths of the viral genome (7494 nucleotides [nt] excluding polyA tail) and short 5'-untranslated region (14 nt) as well as two predicted open reading frames are similar to those of other SaVs...
June 22, 2017: Virus Genes
https://www.readbyqxmd.com/read/28642991/extensive-overlap-of-tropical-rainforest-bacterial-endophytes-between-soil-plant-parts-and-plant-species
#20
Emmanuel Haruna, Noraziah M Zin, Dorsaf Kerfahi, Jonathan M Adams
The extent to which distinct bacterial endophyte communities occur between different plant organs and species is poorly known and has implications for bioprospecting efforts. Using the V3 region of the bacterial 16S ribosomal RNA (rRNA) gene, we investigated the diversity patterns of bacterial endophyte communities of three rainforest plant species, comparing leaf, stem, and root endophytes plus rhizosphere soil community. There was extensive overlap in bacterial communities between plant organs, between replicate plants of the same species, between plant species, and between plant organ and rhizosphere soil, with no consistent clustering by compartment or host plant species...
June 22, 2017: Microbial Ecology
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