scholarly journals Genome Sequence and Global Gene Expression of Q54, a New Phage Species Linking the 936 and c2 Phage Species of Lactococcus lactis

2006 ◽  
Vol 188 (17) ◽  
pp. 6101-6114 ◽  
Author(s):  
Louis-Charles Fortier ◽  
Ali Bransi ◽  
Sylvain Moineau
Keyword(s):  
Gene Expression ◽  
Lactococcus Lactis ◽  
Genomic Sequence ◽  
Global Gene Expression ◽  
Open Reading Frames ◽  
Early Gene ◽  
Structural Protein ◽  
Translational Frameshifting ◽  
First Case ◽  
Tail Protein

ABSTRACT The lytic lactococcal phage Q54 was previously isolated from a failed sour cream production. Its complete genomic sequence (26,537 bp) is reported here, and the analysis indicated that it represents a new Lactococcus lactis phage species. A striking feature of phage Q54 is the low level of similarity of its proteome (47 open reading frames) with proteins in databases. A global gene expression study confirmed the presence of two early gene modules in Q54. The unusual configuration of these modules, combined with results of comparative analysis with other lactococcal phage genomes, suggests that one of these modules was acquired through recombination events between c2- and 936-like phages. Proteolytic cleavage and cross-linking of the major capsid protein were demonstrated through structural protein analyses. A programmed translational frameshift between the major tail protein (MTP) and the receptor-binding protein (RBP) was also discovered. A “shifty stop” signal followed by putative secondary structures is likely involved in frameshifting. To our knowledge, this is only the second report of translational frameshifting (+1) in double-stranded DNA bacteriophages and the first case of translational coupling between an MTP and an RBP. Thus, phage Q54 represents a fascinating member of a new species with unusual characteristics that brings new insights into lactococcal phage evolution.

scholarly journals p90 Ribosomal S6 kinases play a significant role in early gene regulation in the cardiomyocyte response to Gq-protein-coupled receptor stimuli, endothelin-1 and α1-adrenergic receptor agonists

2013 ◽  
Vol 450 (2) ◽  
pp. 351-363 ◽  
Author(s):  
Emre Amirak ◽  
Stephen J. Fuller ◽  
Peter H. Sugden ◽  
Angela Clerk
Keyword(s):  
Gene Expression ◽  
Significant Role ◽  
Adrenergic Receptor ◽  
Global Gene Expression ◽  
Early Gene ◽  
Transcriptomic Response ◽  
Endothelin 1 ◽  
Receptor Agonists ◽  
Adult Rat ◽  
H 51

ERK1/2 (extracellular-signal-regulated kinase 1/2) and their substrates RSKs (p90 ribosomal S6 kinases) phosphorylate different transcription factors, contributing differentially to transcriptomic profiles. In cardiomyocytes ERK1/2 are required for >70% of the transcriptomic response to endothelin-1. In the present study we investigated the role of RSKs in the transcriptomic responses to the Gq-protein-coupled receptor agonists endothelin-1, phenylephrine (a generic α1-adrenergic receptor agonist) and A61603 (α1A-adrenergic receptor selective). Phospho-ERK1/2 and phospho-RSKs appeared in cardiomyocyte nuclei within 2–3 min of stimulation (endothelin-1>A61603≈phenylephrine). All agonists increased nuclear RSK2, but only endothelin-1 increased the nuclear RSK1 content. PD184352 (inhibits ERK1/2 activation) and BI-D1870 (inhibits RSKs) were used to dissect the contribution of RSKs to the endothelin-1-responsive transcriptome. Of the 213 RNAs up-regulated after 1 h, 51% required RSKs for their up-regulation, whereas 29% required ERK1/2 but not RSKs. The transcriptomic response to phenylephrine overlapped with, but was not identical with, endothelin-1. As with endothelin-1, PD184352 inhibited the up-regulation of most phenylephrine-responsive transcripts, but the greater variation in the effects of BI-D1870 suggests that differential RSK signalling influences global gene expression. A61603 induced similar changes in RNA expression in cardiomyocytes as phenylephrine, indicating that the signal was mediated largely through α1A-adrenergic receptors. A61603 also increased expression of immediate early genes in perfused adult rat hearts and, as in cardiomyocytes, up-regulation of the majority of genes was inhibited by PD184352. PD184352 or BI-D1870 prevented the increased surface area induced by endothelin-1 in cardiomyocytes. Thus RSKs play a significant role in regulating cardiomyocyte gene expression and hypertrophy in response to Gq-protein-coupled receptor stimulation.

scholarly journals NORF5/HUG1 Is a Component of theMEC1-Mediated Checkpoint Response to DNA Damage and Replication Arrest in Saccharomyces cerevisiae

1999 ◽  
Vol 19 (10) ◽  
pp. 7041-7049 ◽  
Author(s):  
Munira A. Basrai ◽  
Victor E. Velculescu ◽  
Kenneth W. Kinzler ◽  
Philip Hieter
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Global Gene Expression ◽  
Open Reading Frames ◽  
Ataxia Telangiectasia Mutated ◽  
Checkpoint Response ◽  
Replication Arrest ◽  
Checkpoint Pathway ◽  
Radiation Induced

ABSTRACT Analysis of global gene expression in Saccharomyces cerevisiae by the serial analysis of gene expression technique has permitted the identification of at least 302 previously unidentified transcripts from nonannotated open reading frames (NORFs). Transcription of one of these, NORF5/HUG1 (hydroxyurea and UV and gamma radiation induced), is induced by DNA damage, and this induction requires MEC1, a homolog of the ataxia telangiectasia mutated (ATM) gene. DNA damage-specific induction of HUG1, which is independent of the cell cycle stage, is due to the alleviation of repression by the Crt1p-Ssn6p-Tup1p complex. Overexpression of HUG1 is lethal in combination with a mec1 mutation in the presence of DNA damage or replication arrest, whereas a deletion of HUG1 rescues the lethality due to a mec1 null allele. HUG1 is the first example of a NORF with important biological functional properties and defines a novel component of the MEC1checkpoint pathway.

scholarly journals Complete Genomic Sequence of Bacteriophage B3, a Mu-Like Phage of Pseudomonas aeruginosa

2004 ◽  
Vol 186 (19) ◽  
pp. 6560-6574 ◽  
Author(s):  
Michael D. Braid ◽  
Jennifer L. Silhavy ◽  
Christopher L. Kitts ◽  
Raul J. Cano ◽  
Martha M. Howe
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Dna Sequence ◽  
Genomic Sequence ◽  
Open Reading Frames ◽  
Early Gene ◽  
Bacterial Genomes ◽  
Significant Similarity ◽  
Bacterial Proteins ◽  
Genetic Pool ◽  
Tail Proteins

ABSTRACT Bacteriophage B3 is a transposable phage of Pseudomonas aeruginosa. In this report, we present the complete DNA sequence and annotation of the B3 genome. DNA sequence analysis revealed that the B3 genome is 38,439 bp long with a G+C content of 63.3%. The genome contains 59 proposed open reading frames (ORFs) organized into at least three operons. Of these ORFs, the predicted proteins from 41 ORFs (68%) display significant similarity to other phage or bacterial proteins. Many of the predicted B3 proteins are homologous to those encoded by the early genes and head genes of Mu and Mu-like prophages found in sequenced bacterial genomes. Only two of the predicted B3 tail proteins are homologous to other well-characterized phage tail proteins; however, several Mu-like prophages and transposable phage D3112 encode approximately 10 highly similar proteins in their predicted tail gene regions. Comparison of the B3 genomic organization with that of Mu revealed evidence of multiple genetic rearrangements, the most notable being the inversion of the proposed B3 immunity/early gene region, the loss of Mu-like tail genes, and an extreme leftward shift of the B3 DNA modification gene cluster. These differences illustrate and support the widely held view that tailed phages are genetic mosaics arising by the exchange of functional modules within a diverse genetic pool.

scholarly journals Sequence and Organization of the Neodiprion lecontei Nucleopolyhedrovirus Genome

2004 ◽  
Vol 78 (13) ◽  
pp. 7023-7035 ◽  
Author(s):  
Hilary A. M. Lauzon ◽  
Christopher J. Lucarotti ◽  
Peter J. Krell ◽  
Qili Feng ◽  
Arthur Retnakaran ◽  
...  
Keyword(s):  
Gc Content ◽  
Amino Acid Identity ◽  
Open Reading Frames ◽  
Early Gene ◽  
Structural Protein ◽  
Virus Envelope ◽  
Neodiprion Lecontei ◽  
Culex Nigripalpus ◽  
Virus Envelope Protein ◽  
Host Virus Interactions

ABSTRACT All fully sequenced baculovirus genomes, with the exception of the dipteran Culex nigripalpus nucleopolyhedrovirus (CuniNPV), have previously been from Lepidoptera. This study reports the sequencing and characterization of a hymenopteran baculovirus, Neodiprion lecontei nucleopolyhedrovirus (NeleNPV), from the redheaded pine sawfly. NeleNPV has the smallest genome so far published (81,755 bp) and has a GC content of only 33.3%. It contains 89 potential open reading frames, 43 with baculovirus homologues, 6 identified by conserved domains, and 1 with homology to a densovirus structural protein. Average amino acid identity of homologues ranged from 19.7% with CuniNPV to 24.9% with Spodoptera exigua nucleopolyhedrovirus. The conserved set of baculovirus genes has dropped to 29, since NeleNPV lacks an F protein homologue (ac23/ld130). NeleNPV contains 12 conserved lepidopteran baculovirus genes, including that for DNA binding protein, late expression factor 11 (lef-11), polyhedrin, occlusion derived virus envelope protein-18 (odv-e18), p40, and p45, but lacks 21 others, including lef-3, me53, immediate early gene-1, lef-6, pp31, odv-e66, few polyhedra 25k, odv-e25, protein kinase-1, fibroblast growth factor, and ubiquitin. The lack of identified baculovirus homologues may be due to difficulties in identification, differences in host-virus interactions, or other genes performing similar functions. Gene parity plots showed limited colinearity of NeleNPV with other baculoviruses, and phylogenetic analysis indicates that NeleNPV may have existed before the lepidopteran nucleopolyhedrovirus and granulovirus divergence. The creation of two new Baculoviridae genera to fit hymenopteran and dipteran baculoviruses may be necessary.

scholarly journals Human Cytomegalovirus UL28 and UL29 Open Reading Frames Encode a Spliced mRNA and Stimulate Accumulation of Immediate-Early RNAs

2009 ◽  
Vol 83 (19) ◽  
pp. 10187-10197 ◽  
Author(s):  
Dora P. Mitchell ◽  
John P. Savaryn ◽  
Nathaniel J. Moorman ◽  
Thomas Shenk ◽  
Scott S. Terhune
Keyword(s):  
Gene Expression ◽  
Immediate Early Gene ◽  
Open Reading Frames ◽  
Early Gene ◽  
Immediate Early ◽  
Wild Type Virus ◽  
Pcr Analysis ◽  
Early Gene Expression ◽  
Amino Terminal ◽  
Reading Frames

ABSTRACT We have identified a spliced transcript that contains sequences from the HCMV UL29 and UL28 open reading frames. It contains amino-terminal UL29 sequences followed by UL28 sequences, and it includes a poly(A) signal derived from the 3′-untranslated region following the UL26 open reading frame. UL29/28 RNA is expressed with early kinetics, and a virus containing a FLAG epitope inserted at the amino terminus of UL29 expressed a tagged ∼79-kDa protein, pUL29/28, that was detected at 6 h postinfection. The virus also expressed a less-abundant tagged 41-kDa protein, which corresponds in size to a protein that could be produced by translation of an unspliced UL29/28 transcript. Consistent with this prediction, both unspliced and spliced UL29/28 transcript was present in RNA isolated from polysomes. FLAG-tagged protein from the UL29/28 locus accumulated within nuclear viral replication centers during the early phase of infection. Late after infection it was present in the cytoplasm as well, and the protein was present and resistant to proteinase treatment in partially purified preparations of viral particles. Disruption of the UL29/28 locus by mutation resulted in a 10-fold decrease in the levels of DNA replication along with a similar reduction in virus yield. Quantitative reverse transcription-PCR analysis revealed an ∼2-fold decrease in immediate-early gene expression at 4 to 10 h postinfection compared to the wild-type virus, and transient expression of pUL29/28 activated the major immediate-early promoter. Our results argue that the UL29/28 locus contributes to activation of immediate-early gene expression.

scholarly journals The Thiazole-5-Carboxamide GPS491 Inhibits HIV-1, Adenovirus, and Coronavirus Replication by Altering RNA Processing/Accumulation

Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 60
Author(s):  
Subha Dahal ◽  
Ran Cheng ◽  
Peter K. Cheung ◽  
Terek Been ◽  
Ramy Malty ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Viral Gene Expression ◽  
Dna Amplification ◽  
Early Gene ◽  
Viral Gene ◽  
Structural Protein ◽  
Virus Particles ◽  
Reduced Toxicity ◽  
Hiv 1

Medicinal chemistry optimization of a previously described stilbene inhibitor of HIV-1, 5350150 (2-(2-(5-nitro-2-thienyl)vinyl)quinoline), led to the identification of the thiazole-5-carboxamide derivative (GPS491), which retained potent anti-HIV-1 activity with reduced toxicity. In this report, we demonstrate that the block of HIV-1 replication by GPS491 is accompanied by a drastic inhibition of viral gene expression (IC50 ~ 0.25 µM), and alterations in the production of unspliced, singly spliced, and multiply spliced HIV-1 RNAs. GPS491 also inhibited the replication of adenovirus and multiple coronaviruses. Low µM doses of GPS491 reduced adenovirus infectious yield ~1000 fold, altered virus early gene expression/viral E1A RNA processing, blocked viral DNA amplification, and inhibited late (hexon) gene expression. Loss of replication of multiple coronaviruses (229E, OC43, SARS-CoV2) upon GPS491 addition was associated with the inhibition of viral structural protein expression and the formation of virus particles. Consistent with the observed changes in viral RNA processing, GPS491 treatment induced selective alterations in the accumulation/phosphorylation/function of splicing regulatory SR proteins. Our study establishes that a compound that impacts the activity of cellular factors involved in RNA processing can prevent the replication of several viruses with minimal effect on cell viability.

scholarly journals Varicella-zoster virus early infection but not complete replication is required for the induction of chronic hypersensitivity in rat models of postherpetic neuralgia

2021 ◽  
Vol 17 (7) ◽  
pp. e1009689
Author(s):  
Benjamin E. Warner ◽  
Michael B. Yee ◽  
Mingdi Zhang ◽  
Rebecca S. Hornung ◽  
Benedikt B. Kaufer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Varicella Zoster Virus ◽  
Postherpetic Neuralgia ◽  
Viral Gene Expression ◽  
Viral Reactivation ◽  
Early Gene ◽  
Viral Gene ◽  
Structural Protein ◽  
Regulation Of Expression ◽  
Varicella Zoster

Herpes zoster, the result of varicella-zoster virus (VZV) reactivation, is frequently complicated by difficult-to-treat chronic pain states termed postherpetic neuralgia (PHN). While there are no animal models of VZV-induced pain following viral reactivation, subcutaneous VZV inoculation of the rat causes long-term nocifensive behaviors indicative of mechanical and thermal hypersensitivity. Previous studies using UV-inactivated VZV in the rat model suggest viral gene expression is required for the development of pain behaviors. However, it remains unclear if complete infection processes are needed for VZV to induce hypersensitivity in this host. To further assess how gene expression and replication contribute, we developed and characterized three replication-conditional VZV using a protein degron system to achieve drug-dependent stability of essential viral proteins. Each virus was then assessed for induction of hypersensitivity in rats under replication permissive and nonpermissive conditions. VZV with a degron fused to ORF9p, a late structural protein that is required for virion assembly, induced nocifensive behaviors under both replication permissive and nonpermissive conditions, indicating that complete VZV replication is dispensable for the induction of hypersensitivity. This conclusion was confirmed by showing that a genetic deletion recombinant VZV lacking DNA packaging protein ORF54p still induced prolonged hypersensitivities in the rat. In contrast, VZV with a degron fused to the essential IE4 or IE63 proteins, which are involved in early gene regulation of expression, induced nocifensive behaviors only under replication permissive conditions, indicating importance of early gene expression events for induction of hypersensitivity. These data establish that while early viral gene expression is required for the development of nocifensive behaviors in the rat, complete replication is dispensable. We postulate this model reflects events leading to clinical PHN, in which a population of ganglionic neurons become abortively infected with VZV during reactivation and survive, but host signaling becomes altered in order to transmit ongoing pain.

Phylogenetic relatedness and immediate early gene expression in black-capped chickadees

2012 ◽  
Author(s):  
Christopher B. Sturdy ◽  
Marc T. Avey ◽  
Laurie L. Bloomfield ◽  
Julie E. Elie ◽  
Todd M. Freeberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Phylogenetic Relatedness ◽  
Early Gene Expression

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

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