scholarly journals Cicada endosymbionts contain tRNAs that are processed despite having genomes that lack tRNA processing activities

2018 ◽  
Author(s):  
James T. Van Leuven ◽  
Meng Mao ◽  
Gordon M. Bennett ◽  
John P. McCutcheon
Keyword(s):  
Trna Synthetase ◽  
Essential Genes ◽  
Trna Processing ◽  
Cellular Processes ◽  
Endosymbiotic Bacteria ◽  
Nucleotide Modification ◽  
Computational Annotation ◽  
Genes Encoding ◽  
Trna Halves ◽  
Computational Predictions

Gene loss and genome reduction are defining characteristics of nutritional endosymbiotic bacteria. In extreme cases, even essential genes related to core cellular processes such as replication, transcription, and translation are lost from endosymbiont genomes. Computational predictions on the genomes of the two bacterial symbionts of the cicadaDiceroprocta semicincta, “CandidatusHodgkinia cicadicola” (Alphaproteobacteria) and “Ca. Sulcia muelleri” (Betaproteobacteria), find only 26 and 16 tRNA, and 15 and 10 aminoacyl tRNA synthetase genes, respectively. Furthermore, the original “Ca.Hodgkinia” genome annotation is missing several essential genes involved in tRNA processing, such as RNase P and CCA tRNA nucleotidyltransferase, as well as several RNA editing enzymes required for tRNA maturation. How “Ca. Sulcia” and “Ca. Hodgkinia” preform basic translation-related processes without these genes remains unknown. Here, by sequencing eukaryotic mRNA and total small RNA, we show that the limited tRNA set predicted by computational annotation of “Ca. Sulcia” and “Ca. Hodgkinia” is likely correct. Furthermore, we show that despite the absence of genes encoding tRNA processing activities in the symbiont genomes, symbiont tRNAs have correctly processed 5’ and 3’ ends, and seem to undergo nucleotide modification. Surprisingly, we find that most “Ca. Hodgkinia”and “Ca. Sulcia” tRNAs exist as tRNA halves. Finally, and in contrast with other related insects, we show that cicadas have experienced little horizontal gene transfer that might complement the activities missing from the endosymbiont genomes. We conclude that “Ca. Sulcia” and “Ca. Hodgkinia” tRNAs likely function in bacterial translation, but require host-encoded enzymes to do so.

scholarly journals Cicada Endosymbionts Have tRNAs That Are Correctly Processed Despite Having Genomes That Do Not Encode All of the tRNA Processing Machinery

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
James T. Van Leuven ◽  
Meng Mao ◽  
Denghui D. Xing ◽  
Gordon M. Bennett ◽  
John P. McCutcheon
Keyword(s):  
Trna Synthetase ◽  
Essential Genes ◽  
Trna Genes ◽  
Content Type ◽  
Trna Processing ◽  
Cellular Processes ◽  
Nucleotide Modification ◽  
Genes Encoding ◽  
Eukaryotic Mrnas ◽  
Trna Halves

ABSTRACTGene loss and genome reduction are defining characteristics of endosymbiotic bacteria. The most highly reduced endosymbiont genomes have lost numerous essential genes related to core cellular processes such as replication, transcription, and translation. Computational gene predictions performed for the genomes of the two bacterial symbionts of the cicadaDiceroprocta semicincta, “CandidatusHodgkinia cicadicola” (Alphaproteobacteria) and “Ca. Sulcia muelleri” (Bacteroidetes), have found only 26 and 16 tRNA genes and 15 and 10 aminoacyl tRNA synthetase genes, respectively. Furthermore, the original “Ca. Hodgkinia cicadicola” genome annotation was missing several essential genes involved in tRNA processing, such as those encoding RNase P and CCA tRNA nucleotidyltransferase as well as several RNA editing enzymes required for tRNA maturation. How these cicada endosymbionts perform basic translation-related processes remains unknown. Here, by sequencing eukaryotic mRNAs and total small RNAs, we show that the limited tRNA set predicted by computational annotation of “Ca. Sulcia muelleri” and “Ca. Hodgkinia cicadicola” is likely correct. Furthermore, we show that despite the absence of genes encoding tRNA processing activities in the symbiont genomes, symbiont tRNAs have correctly processed 5′ and 3′ ends and seem to undergo nucleotide modification. Surprisingly, we found that most “Ca. Hodgkinia cicadicola” and “Ca. Sulcia muelleri” tRNAs exist as tRNA halves. We hypothesize that “Ca. Sulcia muelleri” and “Ca. Hodgkinia cicadicola” tRNAs function in bacterial translation but require host-encoded enzymes to do so.IMPORTANCEThe smallest bacterial genomes, in the range of about 0.1 to 0.5 million base pairs, are commonly found in the nutritional endosymbionts of insects. These tiny genomes are missing genes that encode proteins and RNAs required for the translation of mRNAs, one of the most highly conserved and important cellular processes. In this study, we found that the bacterial endosymbionts of cicadas have genomes which encode incomplete tRNA sets and lack genes required for tRNA processing. Nevertheless, we found that endosymbiont tRNAs are correctly processed at their 5′ and 3′ ends and, surprisingly, that mostly exist as tRNA halves. We hypothesize that the cicada host must supply its symbionts with these missing tRNA processing activities.

scholarly journals Structure and expression of the genes encoding the alpha and beta subunits of yeast phenylalanyl-tRNA synthetase.

1988 ◽  
Vol 263 (30) ◽  
pp. 15407-15415
Author(s):  
A Sanni ◽  
M Mirande ◽  
J P Ebel ◽  
Y Boulanger ◽  
J P Waller ◽  
...  
Keyword(s):  
Trna Synthetase ◽  
Beta Subunits ◽  
Genes Encoding

scholarly journals Cross-Predicting Essential Genes between Two Model Eukaryotic Species Using Machine Learning

2021 ◽  
Vol 22 (10) ◽  
pp. 5056
Author(s):  
Tulio L. Campos ◽  
Pasi K. Korhonen ◽  
Neil D. Young
Keyword(s):  
Machine Learning ◽  
Experimental Studies ◽  
Essential Genes ◽  
Subcellular Localisation ◽  
Cross Prediction ◽  
Gene Essentiality ◽  
C Elegans ◽  
Cellular Processes ◽  
Eukaryotic Species ◽  
The Cross

Experimental studies of Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular and cellular processes in metazoans at large. Since the publication of their genomes, functional genomic investigations have identified genes that are essential or non-essential for survival in each species. Recently, a range of features linked to gene essentiality have been inferred using a machine learning (ML)-based approach, allowing essentiality predictions within a species. Nevertheless, predictions between species are still elusive. Here, we undertake a comprehensive study using ML to discover and validate features of essential genes common to both C. elegans and D. melanogaster. We demonstrate that the cross-species prediction of gene essentiality is possible using a subset of features linked to nucleotide/protein sequences, protein orthology and subcellular localisation, single-cell RNA-seq, and histone methylation markers. Complementary analyses showed that essential genes are enriched for transcription and translation functions and are preferentially located away from heterochromatin regions of C. elegans and D. melanogaster chromosomes. The present work should enable the cross-prediction of essential genes between model and non-model metazoans.

scholarly journals Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 10 ◽  
Author(s):  
Pamela Bielli ◽  
Vittoria Pagliarini ◽  
Marco Pieraccioli ◽  
Cinzia Caggiano ◽  
Claudio Sette
Keyword(s):  
Alternative Splicing ◽  
Brain Tumors ◽  
Current Knowledge ◽  
Tumor Biology ◽  
Cancer Therapies ◽  
Cellular Processes ◽  
Genes Encoding ◽  
Targeted Cancer Therapies ◽  
Oncogenic Driver ◽  
Intercellular Communications

Brain tumors are a heterogeneous group of neoplasms ranging from almost benign to highly aggressive phenotypes. The malignancy of these tumors mostly relies on gene expression reprogramming, which is frequently accompanied by the aberrant regulation of RNA processing mechanisms. In brain tumors, defects in alternative splicing result either from the dysregulation of expression and activity of splicing factors, or from mutations in the genes encoding splicing machinery components. Aberrant splicing regulation can generate dysfunctional proteins that lead to modification of fundamental physiological cellular processes, thus contributing to the development or progression of brain tumors. Herein, we summarize the current knowledge on splicing abnormalities in brain tumors and how these alterations contribute to the disease by sustaining proliferative signaling, escaping growth suppressors, or establishing a tumor microenvironment that fosters angiogenesis and intercellular communications. Lastly, we review recent efforts aimed at developing novel splicing-targeted cancer therapies, which employ oligonucleotide-based approaches or chemical modulators of alternative splicing that elicit an impact on brain tumor biology.

scholarly journals Functional genetic encoding of sulfotyrosine in mammalian cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinyuan He ◽  
Yan Chen ◽  
Daisy Guiza Beltran ◽  
Maia Kelly ◽  
Bin Ma ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Biochemical Characterization ◽  
Trna Synthetase ◽  
Functional Verification ◽  
Cellular Processes ◽  
Genetic Encoding ◽  
Efficient Expression

Abstract Protein tyrosine O-sulfation (PTS) plays a crucial role in extracellular biomolecular interactions that dictate various cellular processes. It also involves in the development of many human diseases. Regardless of recent progress, our current understanding of PTS is still in its infancy. To promote and facilitate relevant studies, a generally applicable method is needed to enable efficient expression of sulfoproteins with defined sulfation sites in live mammalian cells. Here we report the engineering, in vitro biochemical characterization, structural study, and in vivo functional verification of a tyrosyl-tRNA synthetase mutant for the genetic encoding of sulfotyrosine in mammalian cells. We further apply this chemical biology tool to cell-based studies on the role of a sulfation site in the activation of chemokine receptor CXCR4 by its ligand. Our work will not only facilitate cellular studies of PTS, but also paves the way for economical production of sulfated proteins as therapeutic agents in mammalian systems.

scholarly journals Rho GTPase Regulators and Effectors in Autism Spectrum Disorders: Animal Models and Insights for Therapeutics

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 835 ◽  
Author(s):  
Daji Guo ◽  
Xiaoman Yang ◽  
Lei Shi
Keyword(s):  
Animal Models ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Autism Spectrum ◽  
Neuronal Morphology ◽  
Nucleotide Exchange ◽  
Cellular Processes ◽  
Research Initiative ◽  
Genes Encoding ◽  
And Function

The Rho family GTPases are small G proteins that act as molecular switches shuttling between active and inactive forms. Rho GTPases are regulated by two classes of regulatory proteins, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Rho GTPases transduce the upstream signals to downstream effectors, thus regulating diverse cellular processes, such as growth, migration, adhesion, and differentiation. In particular, Rho GTPases play essential roles in regulating neuronal morphology and function. Recent evidence suggests that dysfunction of Rho GTPase signaling contributes substantially to the pathogenesis of autism spectrum disorder (ASD). It has been found that 20 genes encoding Rho GTPase regulators and effectors are listed as ASD risk genes by Simons foundation autism research initiative (SFARI). This review summarizes the clinical evidence, protein structure, and protein expression pattern of these 20 genes. Moreover, ASD-related behavioral phenotypes in animal models of these genes are reviewed, and the therapeutic approaches that show successful treatment effects in these animal models are discussed.

scholarly journals Genome-wide screen uncovers novel pathways for tRNA processing and nuclear–cytoplasmic dynamics

2015 ◽  
Vol 29 (24) ◽  
pp. 2633-2644 ◽  
Author(s):  
Jingyan Wu ◽  
Alicia Bao ◽  
Kunal Chatterjee ◽  
Yao Wan ◽  
Anita K. Hopper
Keyword(s):  
Nuclear Export ◽  
Outer Membrane Proteins ◽  
Chromatin Modification ◽  
Mitochondrial Outer Membrane ◽  
Cell Physiology ◽  
Gene Products ◽  
Ribonucleic Acids ◽  
Trna Processing ◽  
Genome Wide ◽  
Genes Encoding

Transfer ribonucleic acids (tRNAs) are essential for protein synthesis. However, key gene products involved in tRNA biogenesis and subcellular movement remain to be discovered. We conducted the first comprehensive unbiased analysis of the role of nearly an entire proteome in tRNA biology and describe 162 novel and 12 previously known Saccharomyces cerevisiae gene products that function in tRNA processing, turnover, and subcellular movement. tRNA nuclear export is of particular interest because it is essential, but the known tRNA exporters (Los1 [exportin-t] and Msn5 [exportin-5]) are unessential. We report that mutations of CRM1 (Exportin-1), MEX67/MTR2 (TAP/p15), and five nucleoporins cause accumulation of unspliced tRNA, a hallmark of defective tRNA nuclear export. CRM1 mutation genetically interacts with los1Δ and causes altered tRNA nuclear–cytoplasmic distribution. The data implicate roles for the protein and mRNA nuclear export machineries in tRNA nuclear export. Mutations of genes encoding actin cytoskeleton components and mitochondrial outer membrane proteins also cause accumulation of unspliced tRNA, likely due to defective splicing on mitochondria. Additional gene products, such as chromatin modification enzymes, have unanticipated effects on pre-tRNA end processing. Thus, this genome-wide screen uncovered putative novel pathways for tRNA nuclear export and extensive links between tRNA biology and other aspects of cell physiology.

Transcriptome Analysis of Listeria monocytogenes Grown on a Ready-to-Eat Meat Matrix

2011 ◽  
Vol 74 (7) ◽  
pp. 1104-1111 ◽  
Author(s):  
DONGRYEOUL BAE ◽  
MICHAEL R. CROWLEY ◽  
CHINLING WANG
Keyword(s):  
Listeria Monocytogenes ◽  
Virulence Factors ◽  
Microarray Data ◽  
Meat Products ◽  
Phospholipid Metabolism ◽  
Transcriptional Level ◽  
Cellular Processes ◽  
Reverse Transcription Pcr ◽  
Expression Of Genes ◽  
Genes Encoding

The contamination of ready-to-eat (RTE) meat products with Listeria monocytogenes is a major concern for the food industry. For a better understanding of the adaptation and survival ability of L. monocytogenes grown on turkey deli meat, the transcriptome of L. monocytogenes strain F2365 was determined with a microarray. Microarray data were validated with a quantitative real-time reverse transcription PCR assay. Based on the microarray data, 39 and 45 genes from L. monocytogenes were transcriptionally upregulated and down-regulated, respectively. The genes regulated at the transcriptional level were mainly involved in energy metabolism, fatty acid and phospholipid metabolism, biosynthesis of proteins, transport and binding proteins, DNA metabolism, cellular processes, and regulatory functions. No significant change was noted for the expression of genes encoding known virulence factors such as sigB, prfA, inlA, inlB, plcA, plcB, and hly. These results suggest that L. monocytogenes grown on RTE deli meat changes its transcription of proteins involved in its metabolic pathways to obtain an energy source or to adapt to environmental change without increasing the expression of virulence factors. The global transcriptome profiles provide a better understanding of the growth or adaptation of L. monocytogenes in RTE meat products.

scholarly journals Differential Expression of Genes Encoding Arabidopsis Phospholipases After Challenge with Virulent or Avirulent Pseudomonas Isolates

2002 ◽  
Vol 15 (8) ◽  
pp. 808-816 ◽  
Author(s):  
Marta de Torres Zabela ◽  
Isabelle Fernandez-Delmond ◽  
Totte Niittyla ◽  
Pedro Sanchez ◽  
Murray Grant
Keyword(s):  
Pseudomonas Syringae ◽  
Defense Responses ◽  
Gene Interactions ◽  
Gene Encoding ◽  
Cellular Processes ◽  
Expression Of Genes ◽  
Pathogen Challenge ◽  
Genes Encoding ◽  
Plant Pathogen Interactions ◽  
Gene For Gene

Phospholipase D (PLD; EC 3.1.4.4) has been linked to a number of cellular processes, including Tran membrane signaling and membrane degradation. Four PLD genes (α, β, γ1, and γ2) have been cloned from Arabidopsis thalami. They encode isoforms with distinct regulatory and catalytic properties but little is known about their physiological roles. Using cDNA amplified fragment length polymorphism display and RNA blot analysis, we identified Arabidopsis PLDγ1 and a gene encoding a lysophospholipase (EC 3.1.1.5), lysoPL1, to be differentially expressed during host response to virulent and avirulent pathogen challenge. Examination of the expression pattern of phospholipase genes induced in response to pathogen challenge was undertaken using the lysoPL1 and gene-specific probes corresponding to the PLD isoforms α, β, and γ1. Each mRNA class exhibited different temporal patterns of expression after infiltration of leaves with Pseudomonas syringae pv. tomato with or without avrRpm1. PLDα was rapidly induced and remained constitutively elevated regardless of treatment. PLDβ was transiently induced upon pathogen challenge. However, mRNA for the lysoPL1 and PLDγ1 genes showed enhanced and sustained elevation during an incompatible interaction, in both ndr1 and overexpressing NahG genetic backgrounds. Further evidence for differential engagement of these PLD mRNA during defense responses, other than gene-for-gene interactions, was demonstrated by their response to salicylic acid treatment or wounding. Our results indicate that genes encoding lysoPL1, PLDγ1, and PLDβ are induced during early responses to pathogen challenge and, additionally, PLDγ1 and lysoPL1 are specifically upregulated during gene-for-gene interactions, leading to the hypersensitive response. We discuss the possible role of these genes in plant-pathogen interactions.

scholarly journals Application of the Subtractive Genomics and Molecular Docking Analysis for the Identification of Novel Putative Drug Targets against Salmonella enterica subsp. enterica serovar Poona

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Tanvir Hossain ◽  
Mohammad Kamruzzaman ◽  
Talita Zahin Choudhury ◽  
Hamida Nooreen Mahmood ◽  
A. H. M. Nurun Nabi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Salmonella Enterica ◽  
Drug Targets ◽  
Subcellular Location ◽  
Essential Genes ◽  
Scoring Functions ◽  
Essential Proteins ◽  
Cellular Processes ◽  
Subtractive Genomics ◽  
Resistance Patterns

The emergence of novel pathogenic strains with increased antibacterial resistance patterns poses a significant threat to the management of infectious diseases. In this study, we aimed at utilizing the subtractive genomic approach to identify novel drug targets against Salmonella enterica subsp. enterica serovar Poona strain ATCC BAA-1673. We employed in silico bioinformatics tools to subtract the strain-specific paralogous and host-specific homologous sequences from the bacterial proteome. The sorted proteome was further refined to identify the essential genes in the pathogenic bacterium using the database of essential genes (DEG). We carried out metabolic pathway and subcellular location analysis of the essential proteins of the pathogen to elucidate the involvement of these proteins in important cellular processes. We found 52 unique essential proteins in the target proteome that could be utilized as novel targets to design newer drugs. Further, we investigated these proteins in the DrugBank databases and 11 of the unique essential proteins showed druggability according to the FDA approved drug bank databases with diverse broad-spectrum property. Molecular docking analyses of the novel druggable targets with the drugs were carried out by AutoDock Vina option based on scoring functions. The results showed promising candidates for novel drugs against Salmonella infections.

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