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"Essential gene

Yassien Badr, Ayaka Okada, Rania Abo-Sakaya, Emad Beshir, Kenji Ohya, Hideto Fukushi
Equine herpesvirus type 1 (EHV-1) UL11 is a 74-amino-acid tegument protein encoded by ORF51 of the EHV-1 genome. EHV-1 UL11 was previously reported by other researchers using the RacL22 and RacH strains to be nonessential for viral replication in cultured cells. Here, we constructed UL11 mutant viruses including a UL11 null mutant and three C-terminal truncated mutants, for further characterization of EHV-1 UL11 using bacterial artificial chromosome (BAC) technology based on the neuropathogenic strain Ab4p...
November 17, 2017: Archives of Virology
Michal Zmudjak, Sofia Shevtsov, Laure D Sultan, Ido Keren, Oren Ostersetzer-Biran
Plant mitochondria are remarkable with respect to the presence of numerous group II introns which reside in many essential genes. The removal of the organellar introns from the coding genes they interrupt is essential for respiratory functions, and is facilitated by different enzymes that belong to a diverse set of protein families. These include maturases and RNA helicases related proteins that function in group II intron splicing in different organisms. Previous studies indicate a role for the nMAT2 maturase and the RNA helicase PMH2 in the maturation of different pre-RNAs in Arabidopsis mitochondria...
November 17, 2017: International Journal of Molecular Sciences
Javiera M Anguita, Claudia Rojas, Pablo A Pastén, Ignacio T Vargas
Biological arsenic oxidation has been suggested as a key biogeochemical process that controls the mobilization and fate of this metalloid in aqueous environments. To the best of our knowledge, only four aerobic chemolithoautotrophic arsenite-oxidizing (CAO) bacteria have been shown to grow via direct arsenic oxidation and to have the essential genes for chemolithoautotrophic arsenite oxidation. In this study, a new CAO bacterium was isolated from a high Andean watershed evidencing natural dissolved arsenic attenuation...
November 16, 2017: Biodegradation
Till Tiso, Petra Sabelhaus, Beate Behrens, Andreas Wittgens, Frank Rosenau, Heiko Hayen, Lars Mathias Blank
Metabolic engineering of microbial cell factories for the production of heterologous secondary metabolites implicitly relies on the intensification of intracellular flux directed toward the product of choice. Apart from reactions following peripheral pathways, enzymes of the central carbon metabolism are usually targeted for the enhancement of precursor supply. In Pseudomonas putida, a Gram-negative soil bacterium, central carbon metabolism, i.e., the reactions required for the synthesis of all 12 biomass precursors, was shown to be regulated at the metabolic level and not at the transcriptional level...
December 2016: Metabolic Engineering Communications
Jovan Mircetic, Antje Dietrich, Maciej Paszkowski-Rogacz, Mechthild Krause, Frank Buchholz
The TP53 gene fulfills a central role in protecting cells from genetic insult. Given this crucial role it might be surprising that p53 itself is not essential for cell survival. Indeed, TP53 is the single most mutated gene across different cancer types. Thus, both a theoretical and a question of significant practical applicability arise: can cells be programmed to make TP53 an essential gene? Here we present a genetic p53 sensor, in which the loss of p53 is coupled to the rise of HSV-TK expression. We show that the sensor can distinguish both p53 knockout and cells expressing a common TP53 cancer mutation from otherwise isogenic TP53 wild-type cells...
November 13, 2017: Nature Communications
Dawit Nigatu, Patrick Sobetzko, Malik Yousef, Werner Henkel
BACKGROUND: Identification of essential genes is not only useful for our understanding of the minimal gene set required for cellular life but also aids the identification of novel drug targets in pathogens. In this work, we present a simple and effective gene essentiality prediction method using information-theoretic features that are derived exclusively from the gene sequences. RESULTS: We developed a Random Forest classifier and performed an extensive model performance evaluation among and within 15 selected bacteria...
November 9, 2017: BMC Bioinformatics
Divya Mistry, Roger P Wise, Julie A Dickerson
Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network...
2017: PloS One
Jun Fujita, Pablo Freire, Cristian Coarfa, Ashley L Benham, Preethi Gunaratne, Michael D Schneider, Marion Dejosez, Thomas P Zwaka
Ronin (THAP11), a DNA-binding protein that evolved from a primordial DNA transposon by molecular domestication, recognizes a hyperconserved promoter sequence to control developmentally and metabolically essential genes in pluripotent stem cells. However, it remains unclear whether Ronin or related THAP proteins perform similar functions in development. Here, we present evidence that Ronin functions within the nascent heart as it arises from the mesoderm and forms a four-chambered organ. We show that Ronin is vital for cardiogenesis during midgestation by controlling a set of critical genes...
November 7, 2017: Cell Reports
Lia Carolina Soares Medeiros, Lilith South, Duo Peng, Juan M Bustamante, Wei Wang, Molly Bunkofske, Natasha Perumal, Fernando Sanchez-Valdez, Rick L Tarleton
Trypanosomatids (order Kinetoplastida), including the human pathogens Trypanosoma cruzi (agent of Chagas disease), Trypanosoma brucei, (African sleeping sickness), and Leishmania (leishmaniasis), affect millions of people and animals globally. T. cruzi is considered one of the least studied and most poorly understood tropical disease-causing parasites, in part because of the relative lack of facile genetic engineering tools. This situation has improved recently through the application of clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) technology, but a number of limitations remain, including the toxicity of continuous Cas9 expression and the long drug marker selection times...
November 7, 2017: MBio
Seth M Daly, Carolyn R Sturge, Christina F Felder-Scott, Bruce L Geller, David E Greenberg
In late 2015, the first example of a transferrable polymyxin resistance mechanism in Gram-negative pathogens, MCR-1, was reported. Since that report, MCR-1 has been described to occur in many Gram-negative pathogens, and the mechanism of MCR-1-mediated resistance was rapidly determined: an ethanolamine is attached to lipid A phosphate groups, rendering the membrane more electropositive and repelling positively charged polymyxins. Acquisition of MCR-1 is clinically significant because polymyxins are frequently last-line antibiotics used to treat extensively resistant organisms, so acquisition of this mechanism might lead to pan-resistant strains...
November 7, 2017: MBio
Jyoti Prava, Pranavathiyani G, Archana Pan
Staphylococcus aureus, the causative agent of nosocomial infections worldwide, has acquired resistance to almost all antibiotics stressing the need to develop novel drugs against this pathogen. In S. aureus N315, 302 genes have been identified as essential genes, indispensable for growth and survival of the pathogen. The functions of 40 proteins encoded by S. aureus essential genes were found to be hypothetical and thus referred as essential hypothetical proteins (EHPs). The present study aims to carry out functional characterization of EHPs using bioinformatics tools/databases, whose performance was assessed by Receiver operating characteristic curve analysis...
October 27, 2017: International Journal of Biological Macromolecules
Ramadevi Prathapam, Tsuyoshi Uehara
Tools to enable genome editing are essential for understanding physiology. Here we report a gene replacement method in Pseudomonas aeruginosa using a temperature-sensitive replicon plasmid that does not require mating or isolation of a merodiploid intermediate. This approach was validated by replacing the non-essential ampD gene with a gentamicin resistance cassette. In addition lpxA and lpxD, both located in a complex gene cluster including multiple downstream essential genes, were inactivated when complemented by each target gene in trans...
November 9, 2017: Journal of Microbiological Methods
Donate Weghorn, Shamil Sunyaev
Cancer genomics efforts have identified genes and regulatory elements driving cancer development and neoplastic progression. From a microevolution standpoint, these are subject to positive selection. Although elusive in current studies, genes whose wild-type coding sequences are needed for tumor growth are also of key interest. They are expected to experience negative selection and stay intact under pressure of incessant mutation. The detection of significantly mutated (or undermutated) genes is completely confounded by the genomic heterogeneity of cancer mutation...
November 6, 2017: Nature Genetics
Rongxin Shen, Lan Wang, Xupeng Liu, Jiang Wu, Weiwei Jin, Xiucai Zhao, Xianrong Xie, Qinlong Zhu, Huiwu Tang, Qing Li, Letian Chen, Yao-Guang Liu
Hybrids between divergent populations commonly show hybrid sterility; this reproductive barrier hinders hybrid breeding of the japonica and indica rice (Oryza sativa L.) subspecies. Here we show that structural changes and copy number variation at the Sc locus confer japonica-indica hybrid male sterility. The japonica allele, Sc-j, contains a pollen-essential gene encoding a DUF1618-domain protein; the indica allele, Sc-i, contains two or three tandem-duplicated ~ 28-kb segments, each carrying an Sc-j-homolog with a distinct promoter...
November 3, 2017: Nature Communications
Shinichi Mizuno, Tadafumi Iino, Hidetoshi Ozawa, Yojiro Arinobu, Yong Chong, Koichi Akashi
In hematopoiesis, the expression of critical genes is regulated in a stage-specific manner to maintain normal hematopoiesis. Notch1 is an essential gene involved in the commitment and development of the T-cell lineage. However, the regulation of Notch1 in hematopoiesis is controversial, particularly at the level of hematopoietic stem cell (HSC). Here, we found that the expression of Notch1 is controlled at the post-transcriptional level in HSCs. HSCs express a considerable level of Notch1 mRNA, but its protein level is very low, suggesting a post-transcriptional suppression for Notch1...
November 2, 2017: International Journal of Hematology
István Bartha, Julia di Iulio, J Craig Venter, Amalio Telenti
A gene can be defined as essential when loss of its function compromises viability of the individual (for example, embryonic lethality) or results in profound loss of fitness. At the population level, identification of essential genes is accomplished by observing intolerance to loss-of-function variants. Several computational methods are available to score gene essentiality, and recent progress has been made in defining essentiality in the non-coding genome. Haploinsufficiency is emerging as a critical aspect of gene essentiality: approximately 3,000 human genes cannot tolerate loss of one of the two alleles...
October 30, 2017: Nature Reviews. Genetics
Walter F Lenoir, Tassica L Lim, Traver Hart
The adaptation of CRISPR/Cas9 systems for pooled library genetic knockout screens in mammalian cells has substantially advanced the state of the art in human functional genomics. Screening panels of cell lines for genes whose knockout imposes a significant fitness defect has dramatically expanded our catalog of high-confidence essential genes, and has already proven useful in identifying tumor-specific essential genes for the development of targeted therapies. However, nonexperts currently lack an easy to use way to access this data and to identify whether their genes of interest are essential across different genetic backgrounds...
October 25, 2017: Nucleic Acids Research
Francesca Boldrin, Giulia Degiacomi, Agnese Serafini, Gaëlle S Kolly, Marcello Ventura, Claudia Sala, Roberta Provvedi, Giorgio Palù, Stewart T Cole, Riccardo Manganelli
A range of regulated gene expression systems has been developed for mycobacteria in the last few years to facilitate the study of essential genes, validate novel drug targets and evaluate their vulnerability. Among these, the TetR/Pip-OFF repressible promoter system was successfully used in several mycobacterial species both in vitro and in vivo. In the first version of the system, the repressible promoter was Pptr , a strong Pip-repressible promoter of Streptomyces pristinaespiralis, which might hamper effective downregulation of genes with a low basal expression level...
October 27, 2017: Microbial Biotechnology
Sabiha Shaik, Amit Ranjan, Sumeet K Tiwari, Arif Hussain, Nishant Nandanwar, Narender Kumar, Savita Jadhav, Torsten Semmler, Ramani Baddam, Mohammed Aminul Islam, Munirul Alam, Lothar H Wieler, Haruo Watanabe, Niyaz Ahmed
Escherichia coli sequence type 131 (ST131), a pandemic clone responsible for the high incidence of extraintestinal pathogenic E. coli (ExPEC) infections, has been known widely for its contribution to the worldwide dissemination of multidrug resistance. Although other ExPEC-associated and extended-spectrum-β-lactamase (ESBL)-producing E. coli clones, such as ST38, ST405, and ST648 have been studied widely, no comparative genomic data with respect to other genotypes exist for ST131. In this study, comparative genomic analysis was performed for 99 ST131 E...
October 24, 2017: MBio
Françoise Bringel, Stéphane Vuilleumier
Engineering organisms for biotechnology applications requires knowledge of their essential genes and associated regulatory networks. A new study of methylotrophic metabolism in Methylobacterium reveals essentiality of the unregulated, off-pathway phosphoribulokinase gene and an unexpected key regulatory role for its product ribulose-1,5-bisphosphate.
October 23, 2017: Current Biology: CB
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