scholarly journals Homeostasis in the Central Dogma of Molecular Biology: the importance of mRNA instability

2019 ◽  
Author(s):  
José E. Pérez-Ortín ◽  
Vicente Tordera ◽  
Sebastián Chávez
Keyword(s):  
Molecular Biology ◽  
Model Organism ◽  
Model Organisms ◽  
Published Data ◽  
Central Dogma ◽  
E Coli ◽  
Response Capacity ◽  
Cultured Human Cells ◽  
The Cost

AbstractCell survival requires the control of biomolecule concentration, i.e. biomolecules should approach homeostasis. With information-carrying macromolecules, the particular concentration variation ranges depend on each type: DNA is not buffered, but mRNA and protein concentrations are homeostatically controlled, which leads to the ribostasis and proteostasis concepts. In recent years, we have studied the particular features of mRNA ribostasis and proteostasis in the model organismS. cerevisiae. Here we extend this study by comparing published data from three other model organisms:E. coli, S. pombeand cultured human cells. We describe how mRNA ribostasis is less strict than proteostasis. A constant ratio appears between the average decay and dilution rates during cell growth for mRNA, but not for proteins. We postulate that this is due to a trade-off between the cost of synthesis and the response capacity. This compromise takes place at the transcription level, but is not possible at the translation level as the high stability of proteins,versusthat of mRNAs, precludes it. We hypothesize that the middle-place role of mRNA in theCentral Dogmaof Molecular Biology and its chemical instability make it more suitable than proteins for the fast changes needed for gene regulation.Graphical Abstract

The Central Importance of E. coli and λ‎ Phage in the New Molecular Biology

2021 ◽  
pp. 130-135
Author(s):  
Thomas E. Schindler
Keyword(s):  
Molecular Biology ◽  
Genetic Recombination ◽  
Model Organism ◽  
Restriction Enzymes ◽  
Model Organisms ◽  
Host Restriction ◽  
E Coli ◽  
Jumping Genes ◽  
K 12 ◽  
Convenient Model

This chapter considers two of the most important legacies of the Lederbergs’ pioneering work: the discoveries of the model organisms that would dominate molecular biology, E. coli and λ‎ bacteriophage. The Lederbergs’ introduction of E. coli as a convenient model organism shifted the direction of molecular genetics. Barbara McClintock’s discovery of jumping genes remained unappreciated for decades, until the field of molecular biology caught up to validate her transposable elements in bacteria. The discovery of restriction enzymes—the molecular scissors for precisely cutting DNA at specific sites, a prerequisite for genetic recombination techniques—emphasized the versatility of bacteriophage λ‎ as a powerful experimental tool. The discovery of specialized transduction by Larry Morse and Esther Lederberg hinted at the mechanisms of “host restriction.” Werner Arber and Daisy Dussoix discovered restriction endonucleases by building upon Esther Lederberg’s research with λ‎ phage and the differences between E. coli B and K-12.

scholarly journals “What You Need, Baby, I Got It”: Transposable Elements as Suppliers of Cis-Operating Sequences in Drosophila

Biology ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 25 ◽  
Author(s):  
Roberta Moschetti ◽  
Antonio Palazzo ◽  
Patrizio Lorusso ◽  
Luigi Viggiano ◽  
René Massimiliano Marsano
Keyword(s):  
Transposable Elements ◽  
Transcriptional Control ◽  
Environmental Changes ◽  
Model Organism ◽  
Model Organisms ◽  
Regulatory Sequences ◽  
Transcriptional Pattern ◽  
Constitutive Components ◽  
Host Genes

Transposable elements (TEs) are constitutive components of both eukaryotic and prokaryotic genomes. The role of TEs in the evolution of genes and genomes has been widely assessed over the past years in a variety of model and non-model organisms. Drosophila is undoubtedly among the most powerful model organisms used for the purpose of studying the role of transposons and their effects on the stability and evolution of genes and genomes. Besides their most intuitive role as insertional mutagens, TEs can modify the transcriptional pattern of host genes by juxtaposing new cis-regulatory sequences. A key element of TE biology is that they carry transcriptional control elements that fine-tune the transcription of their own genes, but that can also perturb the transcriptional activity of neighboring host genes. From this perspective, the transposition-mediated modulation of gene expression is an important issue for the short-term adaptation of physiological functions to the environmental changes, and for long-term evolutionary changes. Here, we review the current literature concerning the regulatory and structural elements operating in cis provided by TEs in Drosophila. Furthermore, we highlight that, besides their influence on both TEs and host genes expression, they can affect the chromatin structure and epigenetic status as well as both the chromosome’s structure and stability. It emerges that Drosophila is a good model organism to study the effect of TE-linked regulatory sequences, and it could help future studies on TE–host interactions in any complex eukaryotic genome.

scholarly journals 120 Role of dynamic base pair polymorphism in the central dogma of molecular biology

2015 ◽  
Vol 33 (sup1) ◽  
pp. 75-76 ◽  
Author(s):  
Isaac J. Kimsey ◽  
Huiqing Zhou ◽  
Heidi Alvey ◽  
Hashim M. Al-Hashimi
Keyword(s):  
Molecular Biology ◽  
Base Pair ◽  
Central Dogma

scholarly journals Role of CheB and CheR in the Complex Chemotactic and Aerotactic Pathway of Azospirillum brasilense

2006 ◽  
Vol 188 (13) ◽  
pp. 4759-4768 ◽  
Author(s):  
Bonnie B. Stephens ◽  
Star N. Loar ◽  
Gladys Alexandre
Keyword(s):  
Escherichia Coli ◽  
Steady State ◽  
Azospirillum Brasilense ◽  
Model Organism ◽  
Spatial Gradient ◽  
Wild Type ◽  
Temporal Gradient ◽  
E Coli ◽  
Significant Difference

ABSTRACT It has previously been reported that the alpha-proteobacterium Azospirillum brasilense undergoes methylation-independent chemotaxis; however, a recent study revealed cheB and cheR genes in this organism. We have constructed cheB, cheR, and cheBR mutants of A. brasilense and determined that the CheB and CheR proteins under study significantly influence chemotaxis and aerotaxis but are not essential for these behaviors to occur. First, we found that although cells lacking CheB, CheR, or both were no longer capable of responding to the addition of most chemoattractants in a temporal gradient assay, they did show a chemotactic response (albeit reduced) in a spatial gradient assay. Second, in comparison to the wild type, cheB and cheR mutants under steady-state conditions exhibited an altered swimming bias, whereas the cheBR mutant and the che operon mutant did not. Third, cheB and cheR mutants were null for aerotaxis, whereas the cheBR mutant showed reduced aerotaxis. In contrast to the swimming bias for the model organism Escherichia coli, the swimming bias in A. brasilense cells was dependent on the carbon source present and cells released methanol upon addition of some attractants and upon removal of other attractants. In comparison to the wild type, the cheB, cheR, and cheBR mutants showed various altered patterns of methanol release upon exposure to attractants. This study reveals a significant difference between the chemotaxis adaptation system of A. brasilense and that of the model organism E. coli and suggests that multiple chemotaxis systems are present and contribute to chemotaxis and aerotaxis in A. brasilense.

scholarly journals Salome Gluecksohn-Waelsch. 6 October 1907—7 November 2007

2019 ◽  
Vol 67 ◽  
pp. 153-171
Author(s):  
Virginia E. Papaioannou
Keyword(s):  
New York ◽  
Molecular Biology ◽  
Model Organism ◽  
Albert Einstein College ◽  
Albert Einstein ◽  
Developmental Genetics ◽  
Developmental Studies ◽  
Columbia University ◽  
Professional Career

Salome Gluecksohn-Waelsch was a pioneer in establishing the field of mammalian developmental genetics, bringing together experimental embryology and genetics at a time when the role of genes in development was far from accepted. She studied in Germany in the 1930s with the renowned experimental embryologist Hans Spemann and then moved to New York City where she spent her entire professional career at Columbia University and the Albert Einstein College of Medicine of Yeshiva University. Her career was remarkable not only for its longevity—she continued experiments well into her 90s—but also for ushering in new ways of approaching developmental biology in mammals. In her studies of the T -complex in mice, she made use of naturally occurring mutations as nature's own experiments that allowed the investigation of the normal role of the genes in the events of morphogenesis. In her later work with the albino chromosomal deletions, she extended her studies to the genetics of physiological traits. Throughout the decades that saw a blossoming of the entire field of genetics, Salome Gluecksohn-Waelsch's work tackling some of the most perplexing problems in mammalian genetics firmly established the mouse as model organism, not only for studying development, but also for the eventual application of molecular biology techniques to development. Her published work is a beautifully coherent and rigorous opus, for which she received many honours. Her influence on a generation of geneticists, developmental biologists and the field of developmental genetics was profound. The life of Salome Gluecksohn–Waelsch spanned a century that suffered the destructive upheaval of two world wars but also saw phenomenal progress in the sciences, including embryology and genetics. At the start of Salome's career, these two fields were far apart and developmental genetics was barely a concept. Along with a few other pioneers, Salome was instrumental in establishing that genes actually had roles in development and in founding the field of mammalian developmental genetics. Her career laid the ground work for the eventual integration of genetic and developmental studies through molecular biology. Salome Gluecksohn–Waelsch published under four different names at different stages of her life and career: Salome Glücksohn, Salome Gluecksohn–Schoenheimer, Salome Gluecksohn–Waelsch, and Salome G. Waelsch. Among her colleagues and friends, she was almost universally known as Salome and so for the purpose of this biographical memoir, I have chosen to refer to her by her first name, out of friendship and respect.

scholarly journals Comparative Study of Cyanobacterial and E. coli RNA Polymerases: Misincorporation, Abortive Transcription, and Dependence on Divalent Cations

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Masahiko Imashimizu ◽  
Kan Tanaka ◽  
Nobuo Shimamoto
Keyword(s):  
Rna Polymerase ◽  
Divalent Cations ◽  
Physiological Role ◽  
Rna Polymerases ◽  
E Coli ◽  
Order Of Magnitude ◽  
Photosynthetic Machinery ◽  
The Difference ◽  
The Cost

If Mg2+ ion is replaced by Mn2+ ion, RNA polymerase tends to misincorporate noncognate nucleotide, which is thought to be one of the reasons for the toxicity of Mn2+ ion. Therefore, most cells have Mn2+ ion at low intracellular concentrations, but cyanobacteria need the ion at a millimolar concentration to maintain photosynthetic machinery. To analyse the mechanism for resistance against the abundant Mn2+ ion, we compared the properties of cyanobacterial and E. coli RNA polymerases. The cyanobacterial enzyme showed a lower level of abortive transcription and less misincorporation than the E. coli enzyme. Moreover, the cyanobacterial enzyme showed a slower rate of the whole elongation by an order of magnitude, paused more frequently, and cleaved its transcript faster in the absence of NTPs. In conclusion, cyanobacterial RNA polymerase maintains the fidelity of transcription against Mn2+ ion by deliberate incorporation of a nucleotide at the cost of the elongation rate. The cyanobacterial and the E. coli enzymes showed different sensitivities to Mg2+ ion, and the physiological role of the difference is also discussed.

scholarly journals Integration of heterogeneous functional genomics data in gerontology research identifies genes and pathway underlying aging across species

2018 ◽  
Author(s):  
Jason A Bubier ◽  
George L Sutphin ◽  
Timothy J Reynolds ◽  
Ron Korstanje ◽  
Axis Fuksman-Kumpa ◽  
...  
Keyword(s):  
Functional Genomics ◽  
Model Organism ◽  
Heterogeneous Data ◽  
Related Genome ◽  
C Elegans ◽  
Gene Sets ◽  
Genome Wide ◽  
Analysis System ◽  
The Cost

Understanding the biological mechanisms behind aging, lifespan and healthspan is becoming increasingly important as the proportion of the world's population over the age of 65 grows, along with the cost and complexity of their care. BigData oriented approaches and analysis methods for integrative functional genomics enable current and future bio-gerontologists to synthesize, distill and interpret vast, heterogeneous data. GeneWeaver is an analysis system for integration of data that allows investigators to store, search, and analyze immense amounts of data including user-submitted experimental data, data from primary publications, and data in other databases. Aging related genome-wide gene sets from primary publications were curated into this system in concert with data from other model-organism and aging-specific databases, and used in several application using GeneWeavers analysis tools. For example, we identified Cd63 as a frequently represented gene among aging-related genome-wide results. To evaluate the role of Cd63 in aging, we performed RNAi knockdown of the C. elegans ortholog, tsp-7, demonstrating that this manipulation is capable of extending lifespan. The tools in GeneWeaver enable aging researchers to make new discoveries into the associations between the genes, normal biological processes, and diseases that affect aging, healthspan, and lifespan.

scholarly journals Are Model Organisms Theoretical Models?

Disputatio ◽  
2017 ◽  
Vol 9 (47) ◽  
pp. 471-498
Author(s):  
Veli-Pekka Parkkinen
Keyword(s):  
Animal Models ◽  
Causal Structure ◽  
Model Organism ◽  
Theoretical Models ◽  
Theoretical Modelling ◽  
Model Organisms ◽  
Target System ◽  
Inductive Step ◽  
Epistemic Role

AbstractThis article compares the epistemic roles of theoretical models and model organisms in science, and specifically the role of non-human animal models in biomedicine. Much of the previous literature on this topic shares an assumption that animal models and theoretical models have a broadly similar epistemic role—that of indirect representation of a target through the study of a surrogate system. Recently, Levy and Currie (2015) have argued that model organism research and theoretical modelling differ in the justification of model-to-target inferences, such that a unified account based on the widely accepted idea of modelling as indirect representation does not similarly apply to both. I defend a similar conclusion, but argue that the distinction between animal models and theoretical models does not always track a difference in the justification of model-to-target inferences. Case studies of the use of animal models in biomedicine are presented to illustrate this. However, Levy and Currie’s point can be argued for in a different way. I argue for the following distinction. Model organisms (and other concrete models) function as surrogate sources of evidence, from which results are transferred to their targets by empirical extrapolation. By contrast, theoretical modelling does not involve such an inductive step. Rather, theoretical models are used for drawing conclusions from what is already known or assumed about the target system. Codifying assumptions about the causal structure of the target in external representational media (e.g. equations, graphs) allows one to apply explicit inferential rules to reach conclusions that could not be reached with unaided cognition alone (cf. Kuorikoski and Ylikoski 2015).

scholarly journals Saccharomyces cerevisiae--a model organism for the studies on vacuolar transport.

2001 ◽  
Vol 48 (4) ◽  
pp. 1025-1042 ◽  
Author(s):  
R Kucharczyk ◽  
J Rytka
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Biology ◽  
Current Knowledge ◽  
Model Organism ◽  
Molecular Transport ◽  
Model System ◽  
Yeast Saccharomyces Cerevisiae ◽  
Vacuolar Transport ◽  
Vacuolar Trafficking

The role of the yeast vacuole, a functional analogue of the mammalian lysosome, in the turnover of proteins and organelles has been well documented. This review provides an overview of the current knowledge of vesicle mediated vacuolar transport in the yeast Saccharomyces cerevisiae cells. Due to the conservation of the molecular transport machinery S. cerevisiae has become an important model system of vacuolar trafficking because of the facile application of genetics, molecular biology and biochemistry.

scholarly journals Ribonucleotide incorporation enables repair of chromosome breaks by nonhomologous end joining

Science ◽  
2018 ◽  
Vol 361 (6407) ◽  
pp. 1126-1129 ◽  
Author(s):  
John M. Pryor ◽  
Michael P. Conlin ◽  
Juan Carvajal-Garcia ◽  
Megan E. Luedeman ◽  
Adam J. Luthman ◽  
...  
Keyword(s):  
Molecular Biology ◽  
Genome Stability ◽  
Nonhomologous End Joining ◽  
Complementary Strand ◽  
End Joining ◽  
Nhej Pathway ◽  
Central Dogma ◽  
Processing Enzymes ◽  
Chromosome Breaks ◽  
The Cost

The nonhomologous end–joining (NHEJ) pathway preserves genome stability by ligating the ends of broken chromosomes together. It employs end-processing enzymes, including polymerases, to prepare ends for ligation. We show that two such polymerases incorporate primarily ribonucleotides during NHEJ—an exception to the central dogma of molecular biology—both during repair of chromosome breaks made by Cas9 and during V(D)J recombination. Moreover, additions of ribonucleotides but not deoxynucleotides effectively promote ligation. Repair kinetics suggest that ribonucleotide-dependent first-strand ligation is followed by complementary strand repair with deoxynucleotides, then by replacement of ribonucleotides embedded in the first strand with deoxynucleotides. Our results indicate that as much as 65% of cellular NHEJ products have transiently embedded ribonucleotides, which promote flexibility in repair at the cost of more fragile intermediates.

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