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Nature Structural & Molecular Biology

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https://www.readbyqxmd.com/read/27892932/reciprocal-regulation-of-carbon-monoxide-metabolism-and-the-circadian-clock
#1
Roman Klemz, Silke Reischl, Thomas Wallach, Nicole Witte, Karsten Jürchott, Sabrina Klemz, Veronika Lang, Stephan Lorenzen, Miriam Knauer, Steffi Heidenreich, Min Xu, Jürgen A Ripperger, Michael Schupp, Ralf Stanewsky, Achim Kramer
Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Feedback of metabolic signals, such as redox state, NAD(+)/NADH and AMP/ADP ratios, or heme, modulate circadian rhythms and thereby optimize energy utilization across the 24-h cycle. We show that rhythmic heme degradation, which generates the signaling molecule carbon monoxide (CO), is required for normal circadian rhythms as well as circadian metabolic outputs. CO suppresses circadian transcription by attenuating CLOCK-BMAL1 binding to target promoters...
November 28, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27870834/position-dependent-termination-and-widespread-obligatory-frameshifting-in-euplotes-translation
#2
Alexei V Lobanov, Stephen M Heaphy, Anton A Turanov, Maxim V Gerashchenko, Sandra Pucciarelli, Raghul R Devaraj, Fang Xie, Vladislav A Petyuk, Richard D Smith, Lawrence A Klobutcher, John F Atkins, Cristina Miceli, Dolph L Hatfield, Pavel V Baranov, Vadim N Gladyshev
The ribosome can change its reading frame during translation in a process known as programmed ribosomal frameshifting. These rare events are supported by complex mRNA signals. However, we found that the ciliates Euplotes crassus and Euplotes focardii exhibit widespread frameshifting at stop codons. 47 different codons preceding stop signals resulted in either +1 or +2 frameshifts, and +1 frameshifting at AAA was the most frequent. The frameshifts showed unusual plasticity and rapid evolution, and had little influence on translation rates...
November 21, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27870833/integrative-classification-of-human-coding-and-noncoding-genes-through-rna-metabolism-profiles
#3
Neelanjan Mukherjee, Lorenzo Calviello, Antje Hirsekorn, Stefano de Pretis, Mattia Pelizzola, Uwe Ohler
Pervasive transcription of the human genome results in a heterogeneous mix of coding RNAs and long noncoding RNAs (lncRNAs). Only a small fraction of lncRNAs have demonstrated regulatory functions, thus making functional lncRNAs difficult to distinguish from nonfunctional transcriptional byproducts. This difficulty has resulted in numerous competing human lncRNA classifications that are complicated by a steady increase in the number of annotated lncRNAs. To address these challenges, we quantitatively examined transcription, splicing, degradation, localization and translation for coding and noncoding human genes...
November 21, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27870832/position-effects-influence-hiv-latency-reversal
#4
Heng-Chang Chen, Javier P Martinez, Eduard Zorita, Andreas Meyerhans, Guillaume J Filion
The main obstacle to curing HIV is the presence of latent proviruses in the bodies of infected patients. The partial success of reactivation therapies suggests that the genomic context of integrated proviruses can interfere with treatment. Here we developed a method called Barcoded HIV ensembles (B-HIVE) to map the chromosomal locations of thousands of individual proviruses while tracking their transcriptional activities in an infected cell population. B-HIVE revealed that, in Jurkat cells, the expression of HIV is strongest close to endogenous enhancers...
November 21, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27820808/oxidative-guanine-base-damage-regulates-human-telomerase-activity
#5
Elise Fouquerel, Justin Lormand, Arindam Bose, Hui-Ting Lee, Grace S Kim, Jianfeng Li, Robert W Sobol, Bret D Freudenthal, Sua Myong, Patricia L Opresko
Changes in telomere length are associated with degenerative diseases and cancer. Oxidative stress and DNA damage have been linked to both positive and negative alterations in telomere length and integrity. Here we examined how the common oxidative lesion 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG) regulates telomere elongation by human telomerase. When 8-oxoG is present in the dNTP pool as 8-oxodGTP, telomerase utilization of the oxidized nucleotide during telomere extension is mutagenic and terminates further elongation...
November 7, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27820807/the-ribosome-engaged-landscape-of-alternative-splicing
#6
Robert J Weatheritt, Timothy Sterne-Weiler, Benjamin J Blencowe
High-throughput RNA sequencing (RNA-seq) has revealed an enormous complexity of alternative splicing (AS) across diverse cell and tissue types. However, it is currently unknown to what extent repertoires of splice-variant transcripts are translated into protein products. Here, we surveyed AS events engaged by the ribosome. Notably, at least 75% of human exon-skipping events detected in transcripts with medium-to-high abundance in RNA-seq data were also detected in ribosome profiling data. Furthermore, relatively small subsets of functionally related splice variants are engaged by ribosomes at levels that do not reflect their absolute abundance, thus indicating a role for AS in modulating translational output...
November 7, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27820806/large-scale-atp-independent-nucleosome-unfolding-by-a-histone-chaperone
#7
Maria E Valieva, Grigoriy A Armeev, Kseniya S Kudryashova, Nadezhda S Gerasimova, Alexey K Shaytan, Olga I Kulaeva, Laura L McCullough, Tim Formosa, Pavel G Georgiev, Mikhail P Kirpichnikov, Vasily M Studitsky, Alexey V Feofanov
DNA accessibility to regulatory proteins is substantially influenced by nucleosome structure and dynamics. The facilitates chromatin transcription (FACT) complex increases the accessibility of nucleosomal DNA, but the mechanism and extent of its nucleosome reorganization activity are unknown. Here we determined the effects of FACT from the yeast Saccharomyces cerevisiae on single nucleosomes by using single-particle Förster resonance energy transfer (spFRET) microscopy. FACT binding results in dramatic ATP-independent, symmetrical and reversible DNA uncoiling that affects at least 70% of the DNA within a nucleosome, occurs without apparent loss of histones and proceeds via an 'all-or-none' mechanism...
November 7, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27798597/cotranscriptional-folding-of-a-riboswitch-at-nucleotide-resolution
#8
Kyle E Watters, Eric J Strobel, Angela M Yu, John T Lis, Julius B Lucks
RNAs can begin to fold immediately as they emerge from RNA polymerase. During cotranscriptional folding, interactions between nascent RNAs and ligands are able to direct the formation of alternative RNA structures, a feature exploited by noncoding RNAs called riboswitches to make gene-regulatory decisions. Despite their importance, cotranscriptional folding pathways have yet to be uncovered with sufficient resolution to reveal how cotranscriptional folding governs RNA structure and function. To access cotranscriptional folding at nucleotide resolution, we extended selective 2'-hydroxyl acylation analyzed by primer-extension sequencing (SHAPE-seq) to measure structural information of nascent RNAs during transcription...
October 31, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27775711/staggered-atp-binding-mechanism-of-eukaryotic-chaperonin-tric-cct-revealed-through-high-resolution-cryo-em
#9
Yunxiang Zang, Mingliang Jin, Huping Wang, Zhicheng Cui, Liangliang Kong, Caixuan Liu, Yao Cong
The eukaryotic chaperonin TRiC (or CCT) assists in the folding of 10% of cytosolic proteins. Here we present two cryo-EM structures of Saccharomyces cerevisiae TRiC in a newly identified nucleotide partially preloaded (NPP) state and in the ATP-bound state, at 4.7-Å and 4.6-Å resolution, respectively. Through inner-subunit eGFP tagging, we identified the subunit locations in open-state TRiC and found that the CCT2 subunit pair forms an unexpected Z shape. ATP binding induces a dramatic conformational change on the CCT2 side, thereby suggesting that CCT2 plays an essential role in TRiC allosteric cooperativity...
October 24, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27775710/ribosome-stalk-biogenesis-is-coupled-with-recruitment-of-nuclear-export-factor-to-the-nascent-60s-subunit
#10
Anshuk Sarkar, Markus Pech, Matthias Thoms, Roland Beckmann, Ed Hurt
Nuclear export of preribosomal subunits is a key step during eukaryotic ribosome formation. To efficiently pass through the FG-repeat meshwork of the nuclear pore complex, the large pre-60S subunit requires several export factors. Here we describe the mechanism of recruitment of the Saccharomyces cerevisiae RNA-export receptor Mex67-Mtr2 to the pre-60S subunit at the proper time. Mex67-Mtr2 binds at the premature ribosomal-stalk region, which later during translation serves as a binding platform for translational GTPases on the mature ribosome...
October 24, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27775709/rna-binding-protein-cpeb1-remodels-host-and-viral-rna-landscapes
#11
Ranjan Batra, Thomas J Stark, Elizabeth Clark, Jean-Philippe Belzile, Emily C Wheeler, Brian A Yee, Hui Huang, Chelsea Gelboin-Burkhart, Stephanie C Huelga, Stefan Aigner, Brett T Roberts, Tomas J Bos, Shashank Sathe, John Paul Donohue, Frank Rigo, Manuel Ares, Deborah H Spector, Gene W Yeo
Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions (3' UTRs) and lengthening of poly(A)-tails in host gene transcripts. We found that the host RNA-binding protein CPEB1 was highly induced after infection, and ectopic expression of CPEB1 in noninfected cells recapitulated infection-related post-transcriptional changes...
October 24, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27723735/regulation-of-ced-3-caspase-localization-and-activation-by-c-elegans-nuclear-membrane-protein-npp-14
#12
Xudong Chen, Yue Wang, Yu-Zen Chen, Brian L Harry, Akihisa Nakagawa, Eui-Seung Lee, Hongyan Guo, Ding Xue
Caspases are cysteine proteases with critical roles in apoptosis. The Caenorhabditis elegans caspase CED-3 is activated by autocatalytic cleavage, a process enhanced by CED-4. Here we report that the CED-3 zymogen localizes to the perinuclear region in C. elegans germ cells and that CED-3 autocatalytic cleavage is held in check by C. elegans nuclei and activated by CED-4. The nuclear-pore protein NPP-14 interacts with the CED-3 zymogen prodomain, colocalizes with CED-3 in vivo and inhibits CED-3 autoactivation in vitro...
October 10, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27694841/structure-of-the-active-form-of-dcp1-dcp2-decapping-enzyme-bound-to-m-7-gdp-and-its-edc3-activator
#13
Clément Charenton, Valerio Taverniti, Claudine Gaudon-Plesse, Régis Back, Bertrand Séraphin, Marc Graille
Elimination of the 5' cap of eukaryotic mRNAs, known as decapping, is considered to be a crucial, irreversible and highly regulated step required for the rapid degradation of mRNA by Xrn1, the major cytoplasmic 5'-3' exonuclease. Decapping is accomplished by the recruitment of a protein complex formed by the Dcp2 catalytic subunit and its Dcp1 cofactor. However, this complex has a low intrinsic enzymatic activity and requires several accessory proteins such as the Lsm1-7 complex, Pat1, Edc1-Edc2 and/or Edc3 to be fully active...
October 3, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27694840/insertion-of-an-alu-element-in-a-lncrna-leads-to-primate-specific-modulation-of-alternative-splicing
#14
Shanshan Hu, Xiaolin Wang, Ge Shan
Noncoding RNAs, mobile elements, and alternative splicing are all critical for the regulation of gene expression. Here we show that a conserved noncoding RNA acquires a new function due to the insertion of a mobile element. We identified a noncoding RNA, termed 5S-OT, which is transcribed from 5S rDNA loci in eukaryotes including fission yeast and mammals. 5S-OT plays a cis role in regulating the transcription of 5S rRNA in mice and humans. In the anthropoidea suborder of primates, an antisense Alu element has been inserted at the 5S-OT locus...
October 3, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27669037/substrate-translocating-loops-regulate-mechanochemical-coupling-and-power-production-in-aaa-protease-clpxp
#15
Piere Rodriguez-Aliaga, Luis Ramirez, Frank Kim, Carlos Bustamante, Andreas Martin
ATP-dependent proteases of the AAA+ family, including Escherichia coli ClpXP and the eukaryotic proteasome, contribute to maintenance of cellular proteostasis. ClpXP unfolds and translocates substrates into an internal degradation chamber, using cycles of alternating dwell and burst phases. The ClpX motor performs chemical transformations during the dwell and translocates the substrate in increments of 1-4 nm during the burst, but the processes occurring during these phases remain unknown. Here we characterized the complete mechanochemical cycle of ClpXP, showing that ADP release and ATP binding occur nonsequentially during the dwell, whereas ATP hydrolysis and phosphate release occur during the burst...
September 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27669036/skywalker-tbc1d24-has-a-lipid-binding-pocket-mutated-in-epilepsy-and-required-for-synaptic-function
#16
Baptiste Fischer, Kevin Lüthy, Jone Paesmans, Charlotte De Koninck, Ine Maes, Jef Swerts, Sabine Kuenen, Valerie Uytterhoeven, Patrik Verstreken, Wim Versées
Mutations in TBC1D24 cause severe epilepsy and DOORS syndrome, but the molecular mechanisms underlying these pathologies are unresolved. We solved the crystal structure of the TBC domain of the Drosophila ortholog Skywalker, revealing an unanticipated cationic pocket conserved among TBC1D24 homologs. Cocrystallization and biochemistry showed that this pocket binds phosphoinositides phosphorylated at the 4 and 5 positions. The most prevalent patient mutations affect the phosphoinositide-binding pocket and inhibit lipid binding...
September 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27669035/e4-ligase-specific-ubiquitination-hubs-coordinate-dna-double-strand-break-repair-and-apoptosis
#17
Leena Ackermann, Michael Schell, Wojciech Pokrzywa, Éva Kevei, Anton Gartner, Björn Schumacher, Thorsten Hoppe
Multiple protein ubiquitination events at DNA double-strand breaks (DSBs) regulate damage recognition, signaling and repair. It has remained poorly understood how the repair process of DSBs is coordinated with the apoptotic response. Here, we identified the E4 ubiquitin ligase UFD-2 as a mediator of DNA-damage-induced apoptosis in a genetic screen in Caenorhabditis elegans. We found that, after initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome...
September 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27669034/dual-interaction-of-the-hsp70-j-protein-cochaperone-zuotin-with-the-40s-and-60s-ribosomal-subunits
#18
Kanghyun Lee, Ruchika Sharma, Om Kumar Shrestha, Craig A Bingman, Elizabeth A Craig
Ribosome-associated J protein-Hsp70 chaperones promote nascent-polypeptide folding and normal translational fidelity. The J protein Zuo1 is known to span the ribosomal subunits, but understanding of its function is limited. Here we present new structural and cross-linking data allowing more precise positioning of Saccharomyces cerevisiae Zuo1 near the 60S polypeptide-exit site and suggesting interactions of Zuo1 with the ribosomal protein eL31 and 25S rRNA helix 24. The junction between the 60S-interacting and subunit-spanning helices is a hinge that positions Zuo1 on the 40S yet accommodates subunit rotation...
September 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27814350/retrotransposons-jump-into-alternative-splicing-regulation-via-a-long-noncoding-rna
#19
Reini F Luco
No abstract text is available yet for this article.
November 4, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27814349/the-membrane-strikes-back-phosphoinositide-binding-regulates-skywalker-function
#20
Steven J Del Signore, Avital A Rodal
No abstract text is available yet for this article.
November 4, 2016: Nature Structural & Molecular Biology
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