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28 papers 0 to 25 followers
https://www.readbyqxmd.com/read/29734690/regulation-of-the-x-chromosome-in-the-germline-and-soma-of-drosophila-melanogaster-males
#1
Eliza Argyridou, John Parsch
During the evolution of heteromorphic sex chromosomes, the sex-specific Y chromosome degenerates, while the X chromosome evolves new mechanisms of regulation. Using bioinformatic and experimental approaches, we investigate the expression of the X chromosome in Drosophila melanogaster . We observe nearly complete X chromosome dosage compensation in male somatic tissues, but not in testis. The X chromosome contains disproportionately fewer genes with high expression in testis than the autosomes, even after accounting for the lack of dosage compensation, which suggests that another mechanism suppresses their expression in the male germline...
May 4, 2018: Genes
https://www.readbyqxmd.com/read/29129640/the-stress-granule-transcriptome-reveals-principles-of-mrna-accumulation-in-stress-granules
#2
Anthony Khong, Tyler Matheny, Saumya Jain, Sarah F Mitchell, Joshua R Wheeler, Roy Parker
Stress granules are mRNA-protein assemblies formed from nontranslating mRNAs. Stress granules are important in the stress response and may contribute to some degenerative diseases. Here, we describe the stress granule transcriptome of yeast and mammalian cells through RNA-sequencing (RNA-seq) analysis of purified stress granule cores and single-molecule fluorescence in situ hybridization (smFISH) validation. While essentially every mRNA, and some noncoding RNAs (ncRNAs), can be targeted to stress granules, the targeting efficiency varies from <1% to >95%...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29191215/domestication-of-self-splicing-introns-during-eukaryogenesis-the-rise-of-the-complex-spliceosomal-machinery
#3
REVIEW
Julian Vosseberg, Berend Snel
ᅟ: The spliceosome is a eukaryote-specific complex that is essential for the removal of introns from pre-mRNA. It consists of five small nuclear RNAs (snRNAs) and over a hundred proteins, making it one of the most complex molecular machineries. Most of this complexity has emerged during eukaryogenesis, a period that is characterised by a drastic increase in cellular and genomic complexity. Although not fully resolved, recent findings have started to shed some light on how and why the spliceosome originated...
December 1, 2017: Biology Direct
https://www.readbyqxmd.com/read/29153837/a-method-for-the-acute-and-rapid-degradation-of-endogenous-proteins
#4
Dean Clift, William A McEwan, Larisa I Labzin, Vera Konieczny, Binyam Mogessie, Leo C James, Melina Schuh
Methods for the targeted disruption of protein function have revolutionized science and greatly expedited the systematic characterization of genes. Two main approaches are currently used to disrupt protein function: DNA knockout and RNA interference, which act at the genome and mRNA level, respectively. A method that directly alters endogenous protein levels is currently not available. Here, we present Trim-Away, a technique to degrade endogenous proteins acutely in mammalian cells without prior modification of the genome or mRNA...
December 14, 2017: Cell
https://www.readbyqxmd.com/read/28864332/associations-of-fats-and-carbohydrate-intake-with-cardiovascular-disease-and-mortality-in-18-countries-from-five-continents-pure-a-prospective-cohort-study
#5
Mahshid Dehghan, Andrew Mente, Xiaohe Zhang, Sumathi Swaminathan, Wei Li, Viswanathan Mohan, Romaina Iqbal, Rajesh Kumar, Edelweiss Wentzel-Viljoen, Annika Rosengren, Leela Itty Amma, Alvaro Avezum, Jephat Chifamba, Rafael Diaz, Rasha Khatib, Scott Lear, Patricio Lopez-Jaramillo, Xiaoyun Liu, Rajeev Gupta, Noushin Mohammadifard, Nan Gao, Aytekin Oguz, Anis Safura Ramli, Pamela Seron, Yi Sun, Andrzej Szuba, Lungiswa Tsolekile, Andreas Wielgosz, Rita Yusuf, Afzal Hussein Yusufali, Koon K Teo, Sumathy Rangarajan, Gilles Dagenais, Shrikant I Bangdiwala, Shofiqul Islam, Sonia S Anand, Salim Yusuf
BACKGROUND: The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear. METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3)...
November 4, 2017: Lancet
https://www.readbyqxmd.com/read/29058725/rational-design-of-proteins-that-exchange-on-functional-timescales
#6
James A Davey, Adam M Damry, Natalie K Goto, Roberto A Chica
Proteins are intrinsically dynamic molecules that can exchange between multiple conformational states, enabling them to carry out complex molecular processes with extreme precision and efficiency. Attempts to design novel proteins with tailored functions have mostly failed to yield efficiencies matching those found in nature because standard methods do not allow the design of exchange between necessary conformational states on a functionally relevant timescale. Here we developed a broadly applicable computational method to engineer protein dynamics that we term meta-multistate design...
December 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28942918/structure-of-fus-protein-fibrils-and-its-relevance-to-self-assembly-and-phase-separation-of-low-complexity-domains
#7
Dylan T Murray, Masato Kato, Yi Lin, Kent R Thurber, Ivan Hung, Steven L McKnight, Robert Tycko
Polymerization and phase separation of proteins containing low-complexity (LC) domains are important factors in gene expression, mRNA processing and trafficking, and localization of translation. We have used solid-state nuclear magnetic resonance methods to characterize the molecular structure of self-assembling fibrils formed by the LC domain of the fused in sarcoma (FUS) RNA-binding protein. From the 214-residue LC domain of FUS (FUS-LC), a segment of only 57 residues forms the fibril core, while other segments remain dynamically disordered...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29066499/a-mutually-exclusive-stem-loop-arrangement-in-rox2-rna-is-essential-for-x-chromosome-regulation-in-drosophila
#8
Ibrahim Avsar Ilik, Daniel Maticzka, Plamen Georgiev, Noel Marie Gutierrez, Rolf Backofen, Asifa Akhtar
The X chromosome provides an ideal model system to study the contribution of RNA-protein interactions in epigenetic regulation. In male flies, roX long noncoding RNAs (lncRNAs) harbor several redundant domains to interact with the ubiquitin ligase male-specific lethal 2 (MSL2) and the RNA helicase Maleless (MLE) for X-chromosomal regulation. However, how these interactions provide the mechanics of spreading remains unknown. By using the uvCLAP (UV cross-linking and affinity purification) methodology, which provides unprecedented information about RNA secondary structures in vivo, we identified the minimal functional unit of roX2 RNA...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28819215/dilution-of-whisky-the-molecular-perspective
#9
Björn C G Karlsson, Ran Friedman
Whisky is distilled to around 70% alcohol by volume (vol-%) then diluted to about 40 vol-%, and often drunk after further slight dilution to enhance its taste. The taste of whisky is primarily associated with amphipathic molecules, such as guaiacol, but why and how dilution enhances the taste is not well understood. We carried out computer simulations of water-ethanol mixtures in the presence of guaiacol, providing atomistic details on the structure of the liquid mixture. We found that guaiacol is preferentially associated with ethanol, and, therefore, primarily found at the liquid-air interface in mixtures that contain up to 45 vol-% of ethanol...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28700573/crispr-cas-encoding-of-a-digital-movie-into-the-genomes-of-a-population-of-living-bacteria
#10
Seth L Shipman, Jeff Nivala, Jeffrey D Macklis, George M Church
DNA is an excellent medium for archiving data. Recent efforts have illustrated the potential for information storage in DNA using synthesized oligonucleotides assembled in vitro. A relatively unexplored avenue of information storage in DNA is the ability to write information into the genome of a living cell by the addition of nucleotides over time. Using the Cas1-Cas2 integrase, the CRISPR-Cas microbial immune system stores the nucleotide content of invading viruses to confer adaptive immunity. When harnessed, this system has the potential to write arbitrary information into the genome...
July 20, 2017: Nature
https://www.readbyqxmd.com/read/28829039/dynamics-and-consequences-of-spliceosome-e-complex-formation
#11
Joshua Donald Larson, Aaron A Hoskins
The spliceosome must identify the correct splice sites (SS) and branchsite (BS) used during splicing. E complex is the earliest spliceosome precursor in which the 5' SS and BS are defined. Definition occurs by U1 small nuclear ribonucleoprotein (snRNP) binding the 5' SS and recognition of the BS by the E complex protein (ECP) branchpoint bridging protein (BBP). We have used single molecule fluorescence to study Saccharomyces cerevisiae U1 and BBP interactions with RNAs. E complex is dynamic and permits frequent redefinition of the 5' SS and BS...
August 22, 2017: ELife
https://www.readbyqxmd.com/read/27813331/sliding-on-dna-from-peptides-to-small-molecules
#12
Kan Xiong, Graham S Erwin, Aseem Z Ansari, Paul C Blainey
Many DNA binding proteins utilize one-dimensional (1D) diffusion along DNA to accelerate their DNA target recognition. Although 1D diffusion of proteins along DNA has been studied for decades, a quantitative understanding is only beginning to emerge and few chemical tools are available to apply 1D diffusion as a design principle. Recently, we discovered that peptides can bind and slide along DNA-even transporting cargo along DNA. Such molecules are known as molecular sleds. Here, to advance our understanding of structure-function relationships governing sequence nonspecific DNA interaction of natural molecular sleds and to explore the potential for controlling sliding activity, we test the DNA binding and sliding activities of chemically modified peptides and analogs, and show that synthetic small molecules can slide on DNA...
November 21, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27603132/therapeutic-targeting-of-splicing-in-cancer
#13
REVIEW
Stanley Chun-Wei Lee, Omar Abdel-Wahab
Recent studies have highlighted that splicing patterns are frequently altered in cancer and that mutations in genes encoding spliceosomal proteins, as well as mutations affecting the splicing of key cancer-associated genes, are enriched in cancer. In parallel, there is also accumulating evidence that several molecular subtypes of cancer are highly dependent on splicing function for cell survival. These findings have resulted in a growing interest in targeting splicing catalysis, splicing regulatory proteins, and/or specific key altered splicing events in the treatment of cancer...
September 7, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27509853/structural-biology-catalytic-spliceosome-captured
#14
COMMENT
Brian Kosmyna, Charles C Query
No abstract text is available yet for this article.
September 8, 2016: Nature
https://www.readbyqxmd.com/read/27509863/capturing-a-substrate-in-an-activated-ring-e3-e2-sumo-complex
#15
Frederick C Streich, Christopher D Lima
Post-translational protein modification by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins such as small ubiquitin-like modifier (SUMO) regulates processes including protein homeostasis, the DNA damage response, and the cell cycle. Proliferating cell nuclear antigen (PCNA) is modified by Ub or poly-Ub at lysine (Lys)164 after DNA damage to recruit repair factors. Yeast PCNA is modified by SUMO on Lys164 and Lys127 during S-phase to recruit the anti-recombinogenic helicase Srs2. Lys164 modification requires specialized E2/E3 enzyme pairs for SUMO or Ub conjugation...
August 18, 2016: Nature
https://www.readbyqxmd.com/read/27485308/evidence-that-birds-sleep-in-mid-flight
#16
Niels C Rattenborg, Bryson Voirin, Sebastian M Cruz, Ryan Tisdale, Giacomo Dell'Omo, Hans-Peter Lipp, Martin Wikelski, Alexei L Vyssotski
Many birds fly non-stop for days or longer, but do they sleep in flight and if so, how? It is commonly assumed that flying birds maintain environmental awareness and aerodynamic control by sleeping with only one eye closed and one cerebral hemisphere at a time. However, sleep has never been demonstrated in flying birds. Here, using electroencephalogram recordings of great frigatebirds (Fregata minor) flying over the ocean for up to 10 days, we show that they can sleep with either one hemisphere at a time or both hemispheres simultaneously...
2016: Nature Communications
https://www.readbyqxmd.com/read/27365453/in-vivo-aspects-of-protein-folding-and-quality-control
#17
REVIEW
David Balchin, Manajit Hayer-Hartl, F Ulrich Hartl
Most proteins must fold into unique three-dimensional structures to perform their biological functions. In the crowded cellular environment, newly synthesized proteins are at risk of misfolding and forming toxic aggregate species. To ensure efficient folding, different classes of molecular chaperones receive the nascent protein chain emerging from the ribosome and guide it along a productive folding pathway. Because proteins are structurally dynamic, constant surveillance of the proteome by an integrated network of chaperones and protein degradation machineries is required to maintain protein homeostasis (proteostasis)...
July 1, 2016: Science
https://www.readbyqxmd.com/read/27259196/easier-better-faster-stronger-improved-methods-for-rna-protein-interaction-studies
#18
COMMENT
Nazmul Haque, J Robert Hogg
The RNA field has been revolutionized by methods that allow genome-scale identification of RNA-protein interaction sites. Two reports now introduce more efficient approaches, opening the technology to wider adoption (Van Nostrand et al., 2016; Zarnegar et al., 2016).
June 2, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27437587/synchronized-cycles-of-bacterial-lysis-for-in-vivo-delivery
#19
M Omar Din, Tal Danino, Arthur Prindle, Matt Skalak, Jangir Selimkhanov, Kaitlin Allen, Ellixis Julio, Eta Atolia, Lev S Tsimring, Sangeeta N Bhatia, Jeff Hasty
The widespread view of bacteria as strictly pathogenic has given way to an appreciation of the prevalence of some beneficial microbes within the human body. It is perhaps inevitable that some bacteria would evolve to preferentially grow in environments that harbor disease and thus provide a natural platform for the development of engineered therapies. Such therapies could benefit from bacteria that are programmed to limit bacterial growth while continually producing and releasing cytotoxic agents in situ. Here we engineer a clinically relevant bacterium to lyse synchronously ata threshold population density and to release genetically encoded cargo...
August 4, 2016: Nature
https://www.readbyqxmd.com/read/27425410/automated-structure-and-sequence-based-design-of-proteins-for-high-bacterial-expression-and-stability
#20
Adi Goldenzweig, Moshe Goldsmith, Shannon E Hill, Or Gertman, Paola Laurino, Yacov Ashani, Orly Dym, Tamar Unger, Shira Albeck, Jaime Prilusky, Raquel L Lieberman, Amir Aharoni, Israel Silman, Joel L Sussman, Dan S Tawfik, Sarel J Fleishman
Upon heterologous overexpression, many proteins misfold or aggregate, thus resulting in low functional yields. Human acetylcholinesterase (hAChE), an enzyme mediating synaptic transmission, is a typical case of a human protein that necessitates mammalian systems to obtain functional expression. We developed a computational strategy and designed an AChE variant bearing 51 mutations that improved core packing, surface polarity, and backbone rigidity. This variant expressed at ∼2,000-fold higher levels in E...
July 21, 2016: Molecular Cell
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