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FORMULATION OF THE PROTEIN SYNTHESIS RATE WITH SEQUENCE INFORMATION

MATHEMATICAL BIOSCIENCES AND ENGINEERING 2018年第2期15卷 507-522页

作者： Xia, Wenjun Lei, Jinzhi Jiangsu Univ Fac Sci Zhenjiang 212013 Jiangsu Peoples R China Tsinghua Univ Zhou Pei Yuan Ctr Appl Math Beijing 100084 Peoples R China

Translation is a central biological process by which proteins are synthesized from genetic information contained within mrnas. Here, we investigate the kinetics of translation at the molecular level by a stochastic simulation model. The model explicitly includes rna sequences, ribosome dynamics, the trna pool and biochemical reactions involved in the translation elongation. The results show that the translation efficiency is mainly limited by the available ribosome number, translation initiation and the translation elongation time. The elongation time is a log-normal distribution, with the mean and variance determined by the codon saturation and the process of aa-trna selection at each codon binding site. Moreover, our simulations show that the translation accuracy exponentially decreases with the sequence length. These results suggest that aa-trna competition is crucial for both translation elongation, translation efficiency and the accuracy, which in turn determined the effective protein production rate of correct proteins. Our results improve the dynamical equation of protein production with a delay differential equation that is dependent on sequence information through both the effective production rate and the distribution of elongation time.

关键词： rna translation efficiency delay differential equation noncoding rna

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The Antisense rna As1_flv4 in the Cyanobacterium Synechocystis sp PCC 6803 Prevents Premature Expression of the flv4-2 Operon upon Shift in Inorganic Carbon Supply

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JOUrnaL OF BIOLOGICAL CHEMISTRY 2012年第40期287卷 33153-33162页

作者： Eisenhut, Marion Georg, Jens Klaehn, Stephan Sakurai, Isamu Mustila, Henna Zhang, Pengpeng Hess, Wolfgang R. Aro, Eva-Mari Univ Turku Dept Biochem & Food Sci FI-20014 Turku Finland Univ Freiburg Fac Biol D-79104 Freiburg Germany

The functional relevance of natural cis-antisense transcripts is mostly unknown. Here we have characterized the association of three antisense rnas and one intergenically encoded noncoding rna with an operon that plays a crucial role in photoprotection of photosystem II under low carbon conditions in the cyanobacterium Synechocystis sp. PCC 6803. Cyanobacteria show strong gene expression dynamics in response to a shift of cells from high carbon to low levels of inorganic carbon (C-i), but the regulatory mechanisms are poorly understood. Among the most up-regulated genes in Synechocystis are flv4, sll0218, and flv2, which are organized in the flv4-2 operon. The flavodiiron proteins encoded by this operon open up an alternative electron transfer route, likely starting from the Q(B) site in photosystem II, under photooxidative stress conditions. Our expression analysis of cells shifted from high carbon to low carbon demonstrated an inversely correlated transcript accumulation of the flv4-2 operon mrna and one antisense rna to flv4, designated as As1_flv4. Overexpression of As1_flv4 led to a decrease in flv4-2 mrna. The promoter activity of as1_flv4 was transiently stimulated by C-i limitation and negatively regulated by the AbrB-like transcription regulator Sll0822, whereas the flv4-2 operon was positively regulated by the transcription factor NdhR. The results indicate that the tightly regulated antisense rna As1_flv4 establishes a transient threshold for flv4-2 expression in the early phase after a change in C-i conditions. Thus, it prevents unfavorable synthesis of the proteins from the flv4-2 operon.

关键词： Antisense rna Cyanobacteria Gene Expression Photosynthesis Photosystem II Ci Regulation Flavodiiron Proteins noncoding rna

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Detection of microrna-335-5p on an Interdigitated Electrode Surface for Determination of the Severity of Abdominal Aortic Aneurysms

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NANOSCALE RESEARCH LETTERS 2020年第1期15卷 105-105页

作者： Lu, Bei Liu, Leiting Wang, Jingrui Chen, Yuan Li, Zhijiang Gopinath, Subash C. B. Lakshmipriya, Thangavel Huo, Zongwei Zhejiang Univ Affiliated Hangzhou First Peoples Hosp Sch Med Dept Hepatopancreatobiliaty Surg Hangzhou 310006 Zhejiang Peoples R China Wuhan 1 Hosp Dept Gen Thorac & Vasc Surg Wuhan 430022 Hubei Peoples R China First Peoples Hosp Zunyi Dept Endocrinol Zunyi 563000 Guizhou Peoples R China Jingmen 1 Peoples Hosp Dept Gallbladder Pancreas & Vasc Surg Jingmen 448000 Hubei Peoples R China Univ Malaysia Perlis Sch Bioproc Engn Arau 02600 Perlis Malaysia Univ Malaysia Perlis Inst Nano Elect Engn Kangar 01000 Perlis Malaysia Shandong First Med Univ & Shandong Acad Med Sci Shandong Canc Hosp & Inst Dept Nucl Med Jinan 250117 Shandong Peoples R China

Abdominal aortic aneurysm (AAA) refers to the enlargement of the lower artery of the abdominal aorta, and identification of an early detection tool is urgently needed for diagnosis. In the current study, an interdigitated electrode (IDE) sensing surface was used to identify mirna-335-5p, which reflects the formation of AAAs. The uniformity of the silica material was observed by 3D profilometry, and the chemically modified highly conductive surface improved the detection via the I-V mode. The targeted mirna-335-5p was detected in a dose-dependent manner and based on linear regression and 3 sigma analyses, the sensitivity was determined to be 1 fM with a biotinylated probe. The high specificity was shown by discriminating the target sequence from noncomplementary and single- and triple-mismatched sequences. These outputs demonstrated the high-performance detection of mirna-335-5p with good reproducibility for determination of the severity of AAA.

关键词： Biosensor noncoding rna Bulging aorta Early diagnosis Streptavidin-biotin

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The callipyge mutation enhances bidirectional long-range DLK1-GTL2 intergenic transcription in cis

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2006年第21期103卷 8119-8124页

作者： Takeda, Haruko Caiment, Florian Smit, Maria Hiard, Samuel Tordoir, Xavier Cockett, Noelle Georges, Michel Charlier, Carole Univ Liege Unit Anim Genet Fac Vet Med B-4000 Liege Belgium Univ Liege CBIG B-4000 Liege Belgium Utah State Univ Coll Agr Logan UT 84322 USA Univ Liege Fac Sci Appl Res Unit Syst & Modelling Dept Elect Engn & Comp Sci B-4000 Liege Belgium

The callipyge mutation (CLPG) is an A to G transition that affects a muscle-specific long-range control element located in the middle of the 90-kb DLK1-GTL2 intergenic (IG) region. It causes ectopic expression of a 327-kb cluster of imprinted genes in skeletal muscle, resulting in the callipyge muscular hypertrophy and its non-Mendelian inheritance pattern known as polar overdominance. We herein demonstrate that the CLPG mutation alters the muscular epigenotype of the DLK1-GTL2 IG region in cis, including hypomethylation, acquisition of novel DINase-1 hypersentivite sites, and, most strikingly, strongly enhanced bidirectional, long-range IG transcription. The callipyge phenotype thus emerges as a unique model to study the functional significance of IG transcription, which recently has proven to be a widespread, yet elusive, feature of the mammalian genome.

关键词： DNA methylation DNase-I hypersensitivity intergenic region noncoding rna

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Epigenetic Mechanisms Underlying the Pathogenesis of Neurogenetic Diseases

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NEUROTHERAPEUTICS 2014年第4期11卷 708-720页

作者： Qureshi, Irfan A. Mehler, Mark F. Albert Einstein Coll Med Roslyn & Leslie Goldstein Lab Stem Cell Biol & Re Bronx NY 10461 USA Albert Einstein Coll Med Inst Brain Disorders & Neural Regenerat Bronx NY 10461 USA Albert Einstein Coll Med Dept Neurol Bronx NY 10461 USA Albert Einstein Coll Med Dept Neurosci Bronx NY 10461 USA Albert Einstein Coll Med Dept Psychiat & Behav Sci Bronx NY 10461 USA Albert Einstein Coll Med Rose F Kennedy Ctr Res Intellectual & Dev Disabil Bronx NY 10461 USA Albert Einstein Coll Med Einstein Canc Ctr Bronx NY 10461 USA Albert Einstein Coll Med Ruth L & David S Gottesman Stem Cell Inst Bronx NY 10461 USA Albert Einstein Coll Med Ctr Epigen Bronx NY 10461 USA Albert Einstein Coll Med Inst Aging Res Bronx NY 10461 USA

There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other health-related phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

关键词： Chromatin DNA methylation Epigenetic Epigenome Histone noncoding rna

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Accelerating Discovery and Functional Analysis of Small rnas with New Technologies

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ANNUAL REVIEW OF GENETICS, VOL 49 2015年第1期49卷 367-394页

作者： Barquist, Lars Vogel, Joerg Univ Wurzburg Inst Mol Infect Biol RNA Biol Grp D-97080 Wurzburg Germany

Over the past decade, bacterial small rnas (srnas) have gone from a biological curiosity to being recognized as a major class of regulatory molecules. High-throughput methods for sampling the transcriptional output of bacterial cells demonstrate that srnas are universal features of bacterial transcriptomes, are plentiful, and appear to vary extensively over evolutionary time. With ever more bacteria coming under study, the question becomes how can we accelerate the discovery and functional characterization of srnas in diverse organisms. New technologies built on high-throughput sequencing are emerging that can rapidly provide global insight into the numbers and functions of srnas in bacteria of interest, providing information that can shape hypotheses and guide research. In this review, we describe recent developments in transcriptomics (rna-seq) and functional genomics that we expect to help us develop an integrated, systems-level view of srna biology in bacteria.

关键词： small rna noncoding rna Hfq rna-seq high-throughput technology TraDIS ribosome profiling phenotype mapping

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An essential role for the DXPas34 tandem repeat and Tsix transcription in the counting process of X chromosome inactivation

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2006年第19期103卷 7390-7395页

作者： Vigneau, Sebastien Augui, Sandrine Navarro, Pablo Avner, Philip Clerc, Philippe Inst Pasteur F-75015 Paris France

A counting process senses the X chromosome/autosome ratio and ensures that X chromosome inactivation (XCl) initiates in the early female (XX) embryo and in differentiating female ES cells but not in their male (XY) counterparts. Counting depends on the X inactivation center (Xic), which contains the Xist gene encoding a nuclear rna, which coats the inactive X chromosome and induces gene silencing. A 37-kb sequence lying 3' to the Xist gene is known to prevent initiation of XCl in male differentiating ES cells. This region contains the major and minor promoters of the Tsix gene, which runs antisense to Xist, and the DXPas34 tandem repeat lying close to the Tsix major promoter. We have addressed the role of these elements in counting by using male ES cells. Targeted deletion of DXPas34 impaired recruitment of rna-polymerase II and TFIIB at the Tsix major promoter, resulting in low levels of Tsix expression in ES cells and moderate ectopic initiation of XCl upon differentiation. A deletion extending 3' to Xist and including the Tsix major promoter resulted in almost complete impairment of Tsix transcription and in efficient ectopic XCl upon differentiation of male ES cells. Internal deletions within the Tsix gene did not affect significantly the level of antisense transcription within Xist and had only minor effects upon differentiation. Our results identify a function for DXPas34 in murine XCl and demonstrate the critical role of Tsix transcription in preventing XCl in differentiating male ES cells and in normal functioning of the counting pathway.

关键词： antisense rna embryonic stem cells noncoding rna silencing x inactivation center

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Unexpected Complexity of the Budding Yeast Transcriptome

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IUBMB LIFE 2008年第12期60卷 775-781页

作者： Ito, Takashi Miura, Fumihito Onda, Miyuki Univ Tokyo Grad Sch Frontier Sci Dept Computat Biol Kashiwa Chiba 2778561 Japan Univ Tokyo Grad Sch Frontier Sci Ctr Om & Bioinformat Kashiwa Chiba 2778561 Japan

The genome of the budding yeast Saccharomyces cerevisiae was sequenced over a decade ago and has been annotated to encode similar to 6,000 genes. However, recent high throughput studies using tiling array hybridization and cDNA sequencing have revealed an unexpectedly large number of previously undescribed transcripts. They largely lack protein-coding capacity and are transcribed from both strands of intragenic and intergenic regions in the genome. Accordingly, pervasive transcription leading to a plethora of noncoding rnas, which was first revealed for mammalian genomes to attract intense attentions, is likely an intrinsic feature of eukaryotic genomes. Although it is not clear what fraction of these transcription events are functional, some were shown to induce transcriptional interference or histone modifications to regulate gene expression. The budding yeast may serve as an excellent model to study pervasive transcription and noncoding rnas. (C) 2008 IUBMB

关键词： noncoding rna antisense transcript transcription start site transcriptional interference histone modification

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The search for a marsupial XIC reveals a break with vertebrate synteny

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CHROMOSOME RESEARCH 2007年第2期15卷 137-146页

作者： Davidow, Lance S. Breen, Matthew Duke, Shannon E. Samollow, Paul B. McCarrey, John R. Lee, Jeannie T. Massachusetts Gen Hosp Dept Mol Biol Boston MA 02114 USA N Carolina State Univ Coll Vet Med Dept Mol Biomed Sci Raleigh NC 27606 USA N Carolina State Univ Coll Vet Med Ctr Comparat Med & Translat Res Raleigh NC 27606 USA Texas A&M Univ Coll Vet Med & Biomed Sci Dept Vet Integrat Biosci College Stn TX 77843 USA Univ Texas Dept Biol San Antonio TX USA Harvard Univ Sch Med Howard Hughes Med Inst Boston MA 02114 USA

X-chromosome inactivation (XCI) evolved in mammals to deal with X-chromosome dosage imbalance between the XX female and the XY male. In eutherian mammals, random XCI of the soma requires a master regulatory locus known as the 'X-inactivation center' (XIC/Xic), wherein lies the noncoding XIST/Xist silencer rna and its regulatory antisense Tsix gene. By contrast, marsupial XCI is imprinted to occur on the paternal X chromosome. To determine whether marsupials and eutherians share the XIC-driven mechanism, we search for the sequence equivalents in the genome of the South American opossum, Monodelphis domestica. Positional cloning and bioinformatic analysis reveal several interesting findings. First, protein-coding genes that flank the eutherian XIC are well-conserved in M. domestica, as well as in chicken, frog, and pufferfish. However, in M. domestica we fail to identify any recognizable XIST or TSIX equivalents. Moreover, cytogenetic mapping shows a surprising break in synteny with eutherian mammals and other vertebrates. Therefore, during the evolution of the marsupial X chromosome, one or more rearrangements broke up an otherwise evolutionarily conserved block of vertebrate genes. The failure to find XIST/TSIX in M. domestica may suggest that the ancestral XIC is too divergent to allow for detection by current methods. Alternatively, the XIC may have arisen relatively late in mammalian evolution, possibly in eutherians with the emergence of random XCI. The latter argues that marsupial XCI does not require XIST and opens the search for alternative mechanisms of dosage compensation.

关键词： marsupial Monodelphis domestica noncoding rna TSIX X-chromosome XIC X inactivation center XIST

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Functional Domains of NEAT1 Architectural lncrna Induce Paraspeckle Assembly through Phase Separation

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MOLECULAR CELL 2018年第6期70卷 1038-+页

作者： Yamazaki, Tomohiro Souquere, Sylvie Chujo, Takeshi Kobelke, Simon Chong, Yee Seng Fox, Archa H. Bond, Charles S. Nakagawa, Shinichi Pierron, Gerard Hirose, Tetsuro Hokkaido Univ Inst Genet Med Sapporo Hokkaido 0600815 Japan Inst Gustave Roussy UMR 8122 CNRS F-94805 Villejuif France Univ Western Australia Sch Human Sci Crawley WA 6009 Australia Univ Western Australia Sch Mol Sci Crawley WA 6009 Australia Hokkaido Univ Fac Pharmaceut Sci Sapporo Hokkaido 0600812 Japan

A class of long noncoding rnas (lncrnas) has architectural functions in nuclear body construction;however, specific rna domains dictating their architectural functions remain uninvestigated. Here, we identified the domains of the architectural NEAT1 lncrna that construct paraspeckles. Systematic deletion of NEAT1 portions using CRISPR/Cas9 in haploid cells revealed modular domains of NEAT1 important for rna stability, isoform switching, and paraspeckle assembly. The middle domain, containing functionally redundant subdomains, was responsible for paraspeckle assembly. Artificial tethering of the NONO protein to a NEAT1_2 mutant lacking the functional subdomains rescued paraspeckle assembly, and this required the NOPS dimerization domain of NONO. Paraspeckles exhibit phase-separated properties including susceptibility to 1,6-hexanediol treatment. rna fragments of the NEAT1_2 subdomains preferentially bound NONO/SFPQ, leading to phase-separated aggregates in vitro. Thus, we demonstrate that the enrichment of NONO dimers on the redundant NEAT1_2 subdomains initiates construction of phase-separated paraspeckles, providing mechanistic insights into lncrna-based nuclear body formation.

关键词： noncoding rna architectural rna nuclear bodies paraspeckle rna-binding proteins prion-like domain phase separation 1 6-hexanediol CRISPR/Cas9 haploid cell

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