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https://www.readbyqxmd.com/read/28935601/ctenopharyngodon-idella-perk-eif2ak3-decreases-cell-viability-by-phosphorylating-eif2%C3%AE-under-er-stress
#1
Tao Zhang, Dongming Li, Lijuan Wan, Xin Chen, Xiangqin Wang, Bin Zhong, Zhen Wu, Huiling Mao, Chengyu Hu
As an upstream kinase of eIF2α, protein kinase RNA-like ER (endoplasmic reticulum) kinase (PERK) is a type I transmembrane protein located in ER in eukaryotic cells. PERK is mainly composed of two domains, the intracavitary domain for BIP protein combination and the dissociative C-terminal region containing a typical serine/threonine kinase domain which promotes the phosphorylation of eIF2α. In this study, we cloned a PERK (also known as EIF2AK3) gene from grass carp (Ctenopharyngodon idella). The full-length cDNA of grass carp PERK (CiPERK) is 5192 bp including a 176 bp of 5' untranslated region, a 1719 bp of 3' untranslated region and a 3297 bp of the longest open reading frame (ORF) encoding 1098 amino acids...
September 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28934489/antisense-oligonucleotides-targeting-translation-inhibitory-elements-in-5-utrs-can-selectively-increase-protein-levels
#2
Xue-Hai Liang, Hong Sun, Wen Shen, Shiyu Wang, Joyee Yao, Michael T Migawa, Huynh-Hoa Bui, Sagar S Damle, Stan Riney, Mark J Graham, Rosanne M Crooke, Stanley T Crooke
A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28924029/circuitry-linking-the-global-csr-and-%C3%AF-e-dependent-cell-envelope-stress-response-systems
#3
Helen Yakhnin, Robert Aichele, Sarah E Ades, Tony Romeo, Paul Babitzke
CsrA of Escherichia coli is an RNA-binding protein that globally regulates a wide variety of cellular processes and behaviors including carbon metabolism, motility, biofilm formation, and the stringent response. CsrB and CsrC are sRNAs that sequester CsrA, thereby preventing CsrA-mRNA interaction. RpoE (σ(E)) is the extracytoplasmic stress response sigma factor of E. coli Previous RNA-seq studies identified rpoE mRNA as a CsrA target. Here we explored the regulation of rpoE by CsrA and found that CsrA represses rpoE translation...
September 18, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28917040/studying-selenoprotein-mrna-translation-using-rna-seq-and-ribosome-profiling
#4
Brian K Dalley, Lisa Baird, Michael T Howard
Deep sequencing of ribosome protected mRNA footprints, also called ribosome profiling or Ribo-Seq, is a relatively new methodology well suited to address questions regarding the mechanisms and efficiency of protein expression. Specifically, the ability of this technique to quantify ribosome abundance with codon resolution enables experiments aimed at studying many aspects of translation, including gene-specific translational efficiency, translation of regulatory upstream short open reading frames, sites of ribosome pausing, and most importantly for selenoproteins, the efficiency by which UGA codons are redefined to encode selenocysteine...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28881981/titer-predicting-translation-initiation-sites-by-deep-learning
#5
Sai Zhang, Hailin Hu, Tao Jiang, Lei Zhang, Jianyang Zeng
Motivation: Translation initiation is a key step in the regulation of gene expression. In addition to the annotated translation initiation sites (TISs), the translation process may also start at multiple alternative TISs (including both AUG and non-AUG codons), which makes it challenging to predict TISs and study the underlying regulatory mechanisms. Meanwhile, the advent of several high-throughput sequencing techniques for profiling initiating ribosomes at single-nucleotide resolution, e...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28851853/translational-repression-of-the-rpos-antiadapter-irad-by-csra-is-mediated-via-translational-coupling-to-a-short-upstream-open-reading-frame
#6
Hongmarn Park, Louise C McGibbon, Anastasia H Potts, Helen Yakhnin, Tony Romeo, Paul Babitzke
CsrA is a global regulatory RNA binding protein that has important roles in regulating carbon metabolism, motility, biofilm formation, and numerous other cellular processes. IraD functions as an antiadapter protein that inhibits RssB-mediated degradation of RpoS, the general stress response and stationary-phase sigma factor of Escherichia coli Here we identified a novel mechanism in which CsrA represses iraD translation via translational coupling. Expression studies with quantitative reverse transcriptase PCR, Western blotting, and lacZ fusions demonstrated that CsrA represses iraD expression...
August 29, 2017: MBio
https://www.readbyqxmd.com/read/28830512/histone-4-lysine-8-acetylation-regulates-proliferation-and-host-pathogen-interaction-in-plasmodium-falciparum
#7
Archana P Gupta, Lei Zhu, Jaishree Tripathi, Michal Kucharski, Alok Patra, Zbynek Bozdech
BACKGROUND: The dynamics of histone modifications in Plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. Here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cycle (IDC) of P. falciparum. RESULTS: Using a dominant-negative transgenic approach, we showed that acetylations of histone H4 play a direct role in transcription. Specifically, these histone modifications mediate an inverse transcriptional relationship between the factors of cell proliferation and host-parasite interaction...
August 22, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28826393/ribosome-profiling-reveals-translational-regulation-of-mammalian-cells-in-response-to-hypoxic-stress
#8
Zhiwen Jiang, Jiaqi Yang, Aimei Dai, Yuming Wang, Wei Li, Zhi Xie
BACKGROUND: Retinal pigment epithelium (RPE) cells transfer oxygen and nutrients from choroid to the neural retina. Reduced oxygen to RPE perturbs development and functions of blood vessels in retina. Previous efforts of genome-wide studies have been largely focused on transcriptional changes of cells in response to hypoxia. Recently developed ribosome profiling provides an opportunity to study genome-wide translational changes. To gain systemic insights into the transcriptional and translational regulation of cellular in response to hypoxic stress, we used simultaneous RNA sequencing and ribosome profiling on an RPE cells line, ARPE-19, under hypoxia condition...
August 21, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28779839/efficient-screening-and-optimization-of-membrane-protein-production-in-escherichia-coli
#9
Jacopo Marino, Katharina Holzhüter, Benedikt Kuhn, Eric R Geertsma
Escherichia coli is one of the most widely used expression hosts for membrane proteins. However, establishing conditions for its recombinant production of membrane proteins remains difficult. Attempts to produce membrane proteins frequently result in either no expression or expression as misfolded aggregates. We developed an efficient pipeline for improving membrane protein overexpression in E. coli that is based on two approaches. The first involves transcriptional fusions, small additional RNA sequences upstream of the target open reading frame, to overcome no or poor overall expression levels...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28747908/unraveling-rubisco-form-i-and-form-ii-regulation-in-an-uncultured-organism-from-a-deep-sea-hydrothermal-vent-via-metagenomic-and-mutagenesis-studies
#10
Stefanie Böhnke, Mirjam Perner
Ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) catalyzes the first major step of carbon fixation in the Calvin-Benson-Bassham (CBB) cycle. This autotrophic CO2 fixation cycle accounts for almost all the assimilated carbon on Earth. Due to the primary role that RubisCO plays in autotrophic carbon fixation, it is important to understand how its gene expression is regulated and the enzyme is activated. Since the majority of all microorganisms are currently not culturable, we used a metagenomic approach to identify genes and enzymes associated with RubisCO expression...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28739310/identification-of-new-tsga10-transcript-variants-in-human-testis-with-conserved-regulatory-rna-elements-in-5-untranslated-region-and-distinct-expression-in-breast-cancer
#11
Pouya Salehipour, Mahsa Nematzadeh, Maryam Beigom Mobasheri, Mandana Afsharpad, Kamran Mansouri, Mohammad Hossein Modarressi
Testis specific gene antigen 10 (TSGA10) is a cancer testis antigen involved in the process of spermatogenesis. TSGA10 could also play an important role in the inhibition of angiogenesis by preventing nuclear localization of HIF-1α. Although it has been shown that TSGA10 messenger RNA (mRNA) is mainly expressed in testis and some tumors, the transcription pattern and regulatory mechanisms of this gene remain largely unknown. Here, we report that human TSGA10 comprises at least 22 exons and generates four different transcript variants...
July 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28732596/structural-and-functional-insights-into-human-re-initiation-complexes
#12
Melanie Weisser, Tanja Schäfer, Marc Leibundgut, Daniel Böhringer, Christopher Herbert Stanley Aylett, Nenad Ban
After having translated short upstream open reading frames, ribosomes can re-initiate translation on the same mRNA. This process, referred to as re-initiation, controls the translation of a large fraction of mammalian cellular mRNAs, many of which are important in cancer. Key ribosomal binding proteins involved in re-initiation are the eukaryotic translation initiation factor 2D (eIF2D) or the homologous complex of MCT-1/DENR. We determined the structures of these factors bound to the human 40S ribosomal subunit in complex with initiator tRNA positioned on an mRNA start codon in the P-site using a combination of cryoelectron microscopy and X-ray crystallography...
August 3, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28668690/in-vivo-development-of-tigecycline-resistance-in-klebsiella-pneumoniae-due-to-deletion-of-ramr-ribosomal-binding-site
#13
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
#14
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
#15
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
#16
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
#17
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...
September 6, 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
#18
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
#19
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-generation-of-nss-deletant-viruses
#20
Benjamin Brennan, Veronica V Rezelj, Richard M Elliott
SFTS phlebovirus (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 nonstructural 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...
August 15, 2017: Journal of Virology
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