Faculty Opinions recommendation of Bacterial translation machinery for deliberate mistranslation of the genetic code.

Author(s):  
Didier Mazel ◽  
José Antonio Escudero Garcia-Calderon
mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Adi Oron-Gottesman ◽  
Martina Sauert ◽  
Isabella Moll ◽  
Hanna Engelberg-Kulka

ABSTRACT Escherichia coli mazEF is an extensively studied stress-induced toxin-antitoxin (TA) system. The toxin MazF is an endoribonuclease that cleaves RNAs at ACA sites. Thereby, under stress, the induced MazF generates a stress-induced translation machinery (STM), composed of MazF-processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Here, we further characterized the STM system, finding that MazF cleaves only ACA sites located in the open reading frames of processed mRNAs, while out-of-frame ACAs are resistant. This in-frame ACA cleavage of MazF seems to depend on MazF binding to an extracellular-death-factor (EDF)-like element in ribosomal protein bS1 (bacterial S1), apparently causing MazF to be part of STM ribosomes. Furthermore, due to the in-frame MazF cleavage of ACAs under stress, a bias occurs in the reading of the genetic code causing the amino acid threonine to be encoded only by its synonym codon ACC, ACU, or ACG, instead of by ACA. IMPORTANCE The genetic code is a universal characteristic of all living organisms. It defines the set of rules by which nucleotide triplets specify which amino acid will be incorporated into a protein. Our results represent the first existing report on a stress-induced bias in the reading of the genetic code. We found that in E. coli , under stress, the amino acid threonine is encoded only by its synonym codon ACC, ACU, or ACG, instead of by ACA. This is because under stress, MazF generates a stress-induced translation machinery (STM) in which MazF cleaves in-frame ACA sites of the processed mRNAs.


Cell Reports ◽  
2016 ◽  
Vol 17 (3) ◽  
pp. 904-916 ◽  
Author(s):  
Alla Gagarinova ◽  
Geordie Stewart ◽  
Bahram Samanfar ◽  
Sadhna Phanse ◽  
Carl A. White ◽  
...  

2000 ◽  
Vol 381 (5-6) ◽  
Author(s):  
M. Sprinzl ◽  
S. Brock ◽  
Y. Huang ◽  
P. Milovnik ◽  
M. Nanninga ◽  
...  

2020 ◽  
Vol 21 (4) ◽  
pp. 311-318
Author(s):  
Akanksha Nigam ◽  
Adi Oron-Gottesman ◽  
Hanna Engelberg-Kulka

Background: Escherichia coli (E. coli) mazEF, a stress-induced toxin-antitoxin (TA) system, has been studied extensively. The MazF toxin is an endoribonuclease that cleaves RNAs at ACA sites. Thereby, under stress, the induced MazF generates a Stress-induced Translation Machinery (STM), composed of MazF processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Materials and Methods: Escherichia coli (E. coli) mazEF, a stress-induced toxin-antitoxin (TA) system, has been studied extensively. The MazF toxin is an endoribonuclease that cleaves RNAs at ACA sites. Thereby, under stress, the induced MazF generates a Stress-induced Translation Machinery (STM), composed of MazF processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Results: Here it is reported that for most of the E. coli proteins mediated by stress-induced MazF, the ACA threonine codon in their mRNAs is not in-frame but rather out-of-frame; in these same RNAs, the three synonymous threonine codons, ACG, ACU, and ACC, are in-frame. In contrast, for proteins translated by the canonical translation system, in the majority of mRNAs, the ACA codon is located in-frame. Conclusion: The described bias in the genetic code is a characteristic of E. coli genes specifying for stress-induced MazF-mediated proteins.


Author(s):  
Sankar Chatterjee ◽  
Surya Yadav

The Late Heavy Bombardment Period (4.1 to 3.8 billion years ago) of heightened impact cratering activity on young Earth is likely the driving force for the origin of life. During the Eoarchean, asteroids such as carbonaceous chondrites delivered the building blocks of life and water to early Earth. Asteroid collisions created innumerable hydrothermal crater lakes in the Eoarchean crust which inadvertently became the perfect cradle for prebiotic chemistry. These hydrothermal crater lakes were filled with cosmic water and the building blocks of life. forming a thick prebiotic soup. The unique combination of exogenous delivery of extraterrestrial building blocks of life, and the endogenous biosynthesis in hydrothermal impact crater lakes very likely gave rise to life. A new symbiotic model for the origin of life within the hydrothermal crater lakes is here proposed. In this scenario, life arose around four billion years ago through five hierarchical stages of increasing molecular complexity: cosmic, geologic, chemical, information, and biological. During the prebiotic synthesis, membranes first appeared in the hydrothermal crater lakes, followed by the simultaneous origin of RNA and protein molecules, creating the RNA/protein world. These proteins were noncoded protein enzymes that facilitated chemical reactions. RNA molecules formed in the hydrothermal crater basin by polymerization of the nucleotides on the montmorillonite mineral substrate. Similarly, the initial synthesis of abiotic protein enzymes was mediated by the condensation of amino acids on pyrite surfaces. The regular wet-dry cycles within the crater lakes assisted further concentration, condensation, and polymerization of the RNAs and proteins. Lipid membranes randomly encapsulated amino acids, RNA, and protein molecules from the prebiotic soup to initiate a molecular symbiosis inside the protocells, this led to the hierarchical emergence of several cell components. As the role of protein enzymes became essential for catalytic process in the RNA/protein world, Darwinian selection from noncoded to coded protein synthesis led to translation systems and the genetic code, heralding the information stage. In this stage, the biochemical pathways suggest the successive emergence of translation machineries such as tRNAs, aaRS, mRNAs, and of ribosomes for protein synthesis. The molecular attraction between tRNA and amino acid led to the emergence of translation machinery and the genetic code.  tRNA is an ancient molecule that created mRNA for the purpose of storing amino acid information like a digital strip. Each mRNA strand became the storage device for genetic information that encoded the amino acid sequences in triplet nucleotides. As information became available in the digital languages of the codon within mRNA, biosynthesis became less random and more organized and directional. The original translation machinery was simpler before the emergence of the ribosome than that of today. We review three main concepts on the origin and evolution of the genetic code: the stereochemical theory, the coevolution theory, and adaptive theory. We believe that these three theories are not mutually exclusive, but are compatible with our coevolution model of translations machines and the genetic code. We suggest biosynthetic pathways as the origin of the translation machine that provided the framework for the origin of the genetic code. During translation, the genetic code developed in three stages coincident with the refinement of the translation machinery: GNC code with four codons and four amino acids during interactions of pre-tRNA/pre-aaRS /pre-mRNA, SNS code consisting of 16 codons and 10 amino acids appeared during the tRNA/aaRS/mRNA interaction, and finally the universal genetic code evolved with the emergence of the tRNA/aaRS/mRNA/ribosome machine. The universal code consists of 64 codons and 20 amino acids, with a redundancy that minimizes errors in translation. To address the question of the origin of the biological information system in the RNA/protein world, we converted letter codons into numerical codons in the Universal Genetic Code Table. We developed a software called CATI (Codon-Amino Acid-Translator-Imitator) to translate randomly chosen numerical codons into corresponding amino acids and vice versa, gaining insight into how translation might have worked in the RNA/protein world. We simulated the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. We used AnyLogic software to simulate and visualize the evolution of the translation machines and the genetic code. We conclude that the emergence of the information age from the RNA/protein world was a watershed event in the origin of life about four billion years ago.


2019 ◽  
pp. 55-68
Author(s):  
V.L. Makarov ◽  
V.G. Grebennikov ◽  
V.E. Dementyev ◽  
E.V. Ustyuzhanina

The debating society “Makarov’s tea party” chaired by the academician V.L. Makarov met on the 18th April 2019 in the Central Economic Mathematical Institute of the Russian Academy of Sciences in order to discuss the interrelationship between ideology and science. The society raised such issues as opposition and interpenetration of science and ideology; ideology and the genetic code of a nation; ideology and manipulation of conscience; numbers and facts as tools of ideological intervention. Here we present the most interesting points of the discussion. The authors of the reports: Makarov Valery, Doctor of Phys.-math., member of the Russian Academy of Sciences; Dementiev Victor, Doctor of Economics, Corr. RAS; Grebennikov Valery, Doctor of Economics; Ustyuzhanina Elena, Doctor of Economics.


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