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https://www.readbyqxmd.com/read/28668690/in-vivo-development-of-tigecycline-resistance-in-klebsiella-pneumoniae-due-to-deletion-of-ramr-ribosomal-binding-site
#1
Meiping Ye, Baixing Ding, Hongliang Qian, Qingqing Xu, Jianping Jiang, Jinwei Huang, Hongyu Ou, Fupin Hu, Minggui Wang
Tigecycline resistance is emerging among Klebsiella pneumoniae isolates, but knowledge on in vivo development of tigecycline resistance is limited. Here, we report a new mechanism of tigecycline resistance in K. pneumoniae which evolved during tigecycline therapy. K. pneumoniae isolates were consecutively obtained from urine samples of a patient with scrotal abscess and urinary tract infection before and during tigecycline treatment. Two tigecycline-resistant K. pneumoniae strains (KP-3R and KP-4R, MIC=8 µg/ml) were isolated after 41 and 47 days of tigecycline therapy...
June 28, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28659957/auxin-signaling-in-regulation-of-plant-translation-reinitiation
#2
REVIEW
Mikhail Schepetilnikov, Lyubov A Ryabova
The mRNA translation machinery directs protein production, and thus cell growth, according to prevailing cellular and environmental conditions. The target of rapamycin (TOR) signaling pathway-a major growth-related pathway-plays a pivotal role in optimizing protein synthesis in mammals, while its deregulation triggers uncontrolled cell proliferation and the development of severe diseases. In plants, several signaling pathways sensitive to environmental changes, hormones, and pathogens have been implicated in post-transcriptional control, and thus far phytohormones have attracted most attention as TOR upstream regulators in plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28655822/translation-initiation-from-conserved-non-aug-codons-provides-additional-layers-of-regulation-and-coding-capacity
#3
Ivaylo P Ivanov, Jiajie Wei, Stephen Z Caster, Kristina M Smith, Audrey M Michel, Ying Zhang, Andrew E Firth, Michael Freitag, Jay C Dunlap, Deborah Bell-Pedersen, John F Atkins, Matthew S Sachs
Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs) in its >700-nucleotide (nt) 5' leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation...
June 27, 2017: MBio
https://www.readbyqxmd.com/read/28639196/specific-increase-of-protein-levels-by-enhancing-translation-using-antisense-oligonucleotides-targeting-upstream-open-frames
#4
Xue-Hai Liang, Wen Shen, Stanley T Crooke
A number of diseases are caused by low levels of key proteins; therefore, increasing the amount of specific proteins in human bodies is of therapeutic interest. Protein expression is downregulated by some structural or sequence elements present in the 5' UTR of mRNAs, such as upstream open reading frames (uORF). Translation initiation from uORF(s) reduces translation from the downstream primary ORF encoding the main protein product in the same mRNA, leading to a less efficient protein expression. Therefore, it is possible to use antisense oligonucleotides (ASOs) to specifically inhibit translation of the uORF by base-pairing with the uAUG region of the mRNA, redirecting translation machinery to initiate from the primary AUG site...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28637336/identification-of-arabidopsis-thaliana-upstream-open-reading-frames-encoding-peptide-sequences-that-cause-ribosomal-arrest
#5
Noriya Hayashi, Shun Sasaki, Hiro Takahashi, Yui Yamashita, Satoshi Naito, Hitoshi Onouchi
Specific sequences of certain nascent peptides cause programmed ribosomal arrest during mRNA translation to control gene expression. In eukaryotes, most known regulatory arrest peptides are encoded by upstream open reading frames (uORFs) present in the 5΄-untranslated region of mRNAs. However, to date, a limited number of eukaryotic uORFs encoding arrest peptides have been reported. Here, we searched for arrest peptide-encoding uORFs among Arabidopsis thaliana uORFs with evolutionarily conserved peptide sequences...
June 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28623304/identification-of-transcripts-with-short-stuorfs-as-targets-for-denr%C3%A2-mcts1-dependent-translation-in-human-cells
#6
Sibylle Schleich, Julieta M Acevedo, Katharina Clemm von Hohenberg, Aurelio A Teleman
The non-canonical initiation factors DENR and MCTS1 have been linked to cancer and autism. We recently showed in Drosophila that DENR and MCTS1 regulate translation re-initiation on transcripts containing upstream Open Reading Frames (uORFs) with strong Kozak sequences (stuORFs). Due to the medical relevance of DENR and MCTS1, it is worthwhile identifying the transcripts in human cells that depend on DENR and MCTS1 for their translation. We show here that in humans, as in Drosophila, transcripts with short stuORFs require DENR and MCTS1 for their optimal expression...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28605958/the-first-report-of-prion-related-protein-gene-prnt-polymorphisms-in-goat
#7
Yong-Chan Kim, Byung-Hoon Jeong
Prion protein is encoded by the prion protein gene (PRNP). Polymorphisms of several members of the prion gene family have shown association with prion diseases in several species. Recent studies on a novel member of the prion gene family in rams have shown that prion-related protein gene (PRNT) has a linkage with codon 26 of prion-like protein (PRND). In a previous study, codon 26 polymorphism of PRND has shown connection with PRNP haplotype which is strongly associated with scrapie vulnerability. In addition, the genotype of a single nucleotide polymorphism (SNP) at codon 26 of PRND is related to fertilisation capacity...
June 2017: Acta Veterinaria Hungarica
https://www.readbyqxmd.com/read/28592543/mapping-of-transcription-termination-within-the-s-segment-of-sfts-phlebovirus-facilitated-the-generation-of-nss-deletant-viruses
#8
Benjamin Brennan, Veronica V Rezelj, Richard M Elliott
SFTS phlebovirus (severe fever with thrombocytopenia syndrome virus; SFTSV) is an emerging tick-borne bunyavirus that was first reported in China in 2009. Here we report the generation of a recombinant SFTSV (rHB29NSsKO) that cannot express the viral non-structural protein (NSs) upon infection of cells in culture. We show that rHB29NSsKO replication kinetics are greater in interferon (IFN)-incompetent cells and that the virus is unable to suppress IFN induced in response to viral replication. The data confirm for the first time in the context of virus infection that NSs acts as a virally encoded IFN antagonist and that NSs is dispensable for virus replication...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28541577/eif1-modulates-the-recognition-of-suboptimal-translation-initiation-sites-and-steers-gene-expression-via-uorfs
#9
Daria Fijalkowska, Steven Verbruggen, Elvis Ndah, Veronique Jonckheere, Gerben Menschaert, Petra Van Damme
Alternative translation initiation mechanisms such as leaky scanning and reinitiation potentiate the polycistronic nature of human transcripts. By allowing for reprogrammed translation, these mechanisms can mediate biological responses to stimuli. We combined proteomics with ribosome profiling and mRNA sequencing to identify the biological targets of translation control triggered by the eukaryotic translation initiation factor 1 (eIF1), a protein implicated in the stringency of start codon selection. We quantified expression changes of over 4000 proteins and 10 000 actively translated transcripts, leading to the identification of 245 transcripts undergoing translational control mediated by upstream open reading frames (uORFs) upon eIF1 deprivation...
May 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28521011/translation-initiation-events-on-structured-eukaryotic-mrnas-generate-gene-expression-noise
#10
Estelle Dacheux, Naglis Malys, Xiang Meng, Vinoy Ramachandran, Pedro Mendes, John Eg McCarthy
Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem-loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28514448/uorf-mediated-translation-allows-engineered-plant-disease-resistance-without-fitness-costs
#11
Guoyong Xu, Meng Yuan, Chaoren Ai, Lijing Liu, Edward Zhuang, Sargis Karapetyan, Shiping Wang, Xinnian Dong
Controlling plant disease has been a struggle for humankind since the advent of agriculture. Studies of plant immune mechanisms have led to strategies of engineering resistant crops through ectopic transcription of plants' own defence genes, such as the master immune regulatory gene NPR1 (ref. 1). However, enhanced resistance obtained through such strategies is often associated with substantial penalties to fitness, making the resulting products undesirable for agricultural applications. To remedy this problem, we sought more stringent mechanisms of expressing defence proteins...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28494858/mtorc1-balances-cellular-amino-acid-supply-with-demand-for-protein-synthesis-through-post-transcriptional-control-of-atf4
#12
Yeonwoo Park, Andrea Reyna-Neyra, Lucas Philippe, Carson C Thoreen
The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4), a key effector of the integrated stress response. ATF4 translation is normally induced by the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) through a mechanism that requires upstream open reading frames (uORFs) in the ATF4 5' UTR...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28484048/novel-translation-initiation-regulation-mechanism-in-escherichia-coli-ptrb-mediated-by-a-5-terminal-aug
#13
Heather J Beck, Gary R Janssen
Alternative translation initiation mechanisms, distinct from the Shine-Dalgarno (SD) sequence-dependent mechanism, are more prevalent in bacteria than once anticipated. Translation of Escherichia coliptrB instead requires an AUG triplet at the 5' terminus of its mRNA. The 5'-terminal AUG (5'-uAUG) acts as a ribosomal recognition signal to attract ribosomes to the ptrB mRNA rather than functioning as an initiation codon to support translation of an upstream open reading frame. ptrB expression exhibits a stronger dependence on the 5'-uAUG than the predicted SD sequence; however, strengthening the predicted ptrB SD sequence relieves the necessity for the 5'-uAUG...
July 15, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28481333/regulation-of-pfemp1-var2csa-translation-by-a-plasmodium-translation-enhancing-factor
#14
Sherwin Chan, Alejandra Frasch, Chandra Sekhar Mandava, Jun-Hong Ch'ng, Maria Del Pilar Quintana, Mattias Vesterlund, Mehdi Ghorbal, Nicolas Joannin, Oscar Franzén, Jose-Juan Lopez-Rubio, Sonia Barbieri, Antonio Lanzavecchia, Suparna Sanyal, Mats Wahlgren
Pregnancy-associated malaria commonly involves the binding of Plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate A (CSA) through the PfEMP1-VAR2CSA protein. VAR2CSA is translationally repressed by an upstream open reading frame. In this study, we report that the P. falciparum translation enhancing factor (PTEF) relieves upstream open reading frame repression and thereby facilitates VAR2CSA translation. VAR2CSA protein levels in var2csa-transcribing parasites are dependent on the expression level of PTEF, and the alleviation of upstream open reading frame repression requires the proteolytic processing of PTEF by PfCalpain...
May 8, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28461717/molecular-cloning-and-characterization-of-s-adenosylmethionine-decarboxylase-gene-in-rubber-tree-hevea-brasiliensis
#15
Manman Zhao, Hui Liu, Zhi Deng, Jiangshu Chen, Hong Yang, Huiping Li, Zhihui Xia, Dejun Li
S-Adenosylmethionine decarboxylase (SAMDC) is a key rate-limiting enzyme involved in polyamines biosynthesis, and it plays important roles in plant growth, development and stresses response. However, no SAMDC gene was reported in rubber tree. Here we report characteristics of an SAMDC gene (HbSAMDC1) in rubber tree. HbSAMDC1 contains a 1080 bp open reading frame (ORF) encoding 359 amino acids. Quantitative real-time PCR analyses revealed that HbSAMDC1 exhibited distinct expression patterns in different tissues and was regulated by various stresses, including drought, cold, salt, wounding, and H2O2 treatments...
April 2017: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
https://www.readbyqxmd.com/read/28461625/transcript-specific-characteristics-determine-the-contribution-of-endo-and-exonucleolytic-decay-pathways-during-the-degradation-of-nonsense-mediated-decay-substrates
#16
Franziska Ottens, Volker Boehm, Christopher R Sibley, Jernej Ule, Niels H Gehring
Nonsense-mediated mRNA decay (NMD) controls gene expression by eliminating mRNAs with premature or aberrant translation termination. Degradation of NMD substrates is initiated by the central NMD factor UPF1, which recruits the endonuclease SMG6 and the deadenylation-promoting SMG5/7 complex. The extent to which SMG5/7 and SMG6 contribute to the degradation of individual substrates and their regulation by UPF1 remain elusive. Here we map transcriptome-wide sites of SMG6-mediated endocleavage via 3' fragment capture and degradome sequencing...
May 1, 2017: RNA
https://www.readbyqxmd.com/read/28459876/alternative-oxidase-aox-constitutes-a-small-family-of-proteins-in-citrus-clementina-and-citrus-sinensis-l-osb
#17
Jacqueline Araújo Castro, Monique Drielle Gomes Ferreira, Raner José Santana Silva, Bruno Silva Andrade, Fabienne Micheli
The alternative oxidase (AOX) protein is present in plants, fungi, protozoa and some invertebrates. It is involved in the mitochondrial respiratory chain, providing an alternative route for the transport of electrons, leading to the reduction of oxygen to form water. The present study aimed to characterize the family of AOX genes in mandarin (Citrus clementina) and sweet orange (Citrus sinensis) at nucleotide and protein levels, including promoter analysis, phylogenetic analysis and C. sinensis gene expression...
2017: PloS One
https://www.readbyqxmd.com/read/28450857/the-functional-roles-of-the-cis-acting-elements-in-bamboo-mosaic-virus-rna-genome
#18
REVIEW
I-Hsuan Chen, Ying-Wen Huang, Ching-Hsiu Tsai
Bamboo mosaic virus (BaMV), which belongs to the genus Potexvirus in the family Alphaflexiviridae, has a single-stranded positive-sense RNA genome that is approximately 6400 nucleotides (nts) in length. Positive-sense RNA viruses can use genomic RNA as a template for translation and replication after entering a suitable host cell. Furthermore, such viral RNA is recognized by capsid protein for packaging and by viral movement protein(s) or the movement protein complex for cell-to-cell and systemic movement. Hence, viral RNA must contain signals for different functions to complete the viral infection cycle...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28445614/two-common-human-cldn5-alleles-encode-different-open-reading-frames-but-produce-one-protein-isoform
#19
Ronald M Cornely, Barbara Schlingmann, Whitney S Shepherd, Joshua D Chandler, David C Neujahr, Michael Koval
Claudins provide tight junction barrier selectivity. The human CLDN5 gene contains a high-frequency single-nucleotide polymorphism (rs885985), where the G allele codes for glutamine (Q) and the A allele codes for an amber stop codon. Thus, these different CLDN5 alleles define nested open reading frames (ORFs) encoding claudin-5 proteins that are 303 or 218 amino acids in length. Interestingly, human claudin-16 and claudin-23 also have long ORFs. The long form of claudin-5 contrasts with the majority of claudin-5 proteins in the National Center for Biotechnology Information protein database, which are less than 220 amino acids in length...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28420619/analysis-of-variants-in-upstream-open-reading-frames-of-human-globin-related-genes
#20
Ye Yuhua, Zhang Qianqian, Zhong Jianmei, Li Yihong, Zhang Li, Yu Qiuxia, Xu Xiangmin
β-thalassemia is an autosomal recessive monogenic disease that is caused by defects in the production of β-like globin chains. Activation of γ-globin gene and the increase in fetal hemoglobin expression have been demonstrated as one of the most important factors to ameliorate the clinical outcome of β-thalassemia patients. In this study, 202 genes or miRNAs associated with human hemoglobin gene expression from 1802 β-thalassemia patients were analyzed with target capture and next generation sequencing strategies in terms of functional variants that might affect hemoglobin gene expression...
March 20, 2017: Yi Chuan, Hereditas
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