scholarly journals Non-enzymatic assembly of active chimeric ribozymes from aminoacylated RNA oligonucleotides

2021 ◽  
Author(s):  
Aleksandar Radakovic ◽  
Saurja Dasgupta ◽  
Tom H Wright ◽  
Harry R.M. Aitken ◽  
Jack W Szostak
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Ribosomal Protein ◽  
Rna World ◽  
Directed Assembly ◽  
Enzymatic Function ◽  
Hammerhead Rna ◽  
Rna Backbone ◽  
Ribosomal Protein Synthesis

Aminoacylated tRNAs, which harbor a covalent linkage between amino acids and RNA, are a universally conserved feature of life. Because they are essential substrates for ribosomal translation, aminoacylated oligonucleotides must have been present in the RNA World prior to the evolution of the ribosome. One possibility we are exploring is that the aminoacyl ester linkage served another function before being recruited for ribosomal protein synthesis. The nonenzymatic assembly of ribozymes from short RNA oligomers under realistic conditions remains a key challenge in demonstrating a plausible pathway from prebiotic chemistry to the RNA World. Here, we show that aminoacylated RNAs can undergo template-directed assembly into chimeric amino acid-RNA polymers that are active ribozymes. We demonstrate that such chimeric polymers can retain the enzymatic function of their all-RNA counterparts by generating chimeric hammerhead, RNA ligase, and aminoacyl transferase ribozymes. Amino acids with diverse side chains form linkages that are well tolerated within the RNA backbone, potentially bringing novel functionalities to ribozyme catalysis. Our work suggests that aminoacylation chemistry may have played a role in primordial ribozyme assembly. Increasing the efficiency of this process provides an evolutionary rationale for the emergence of sequence and amino acid specific aminoacyl-RNA synthetase ribozymes, which could then have generated the substrates for ribosomal protein synthesis.

scholarly journals Ribosomal protein synthesis is decreased in tauopathy as revealed by noncanonical amino acid labelling

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Harrison Tudor Evans ◽  
Joseph Benetatos ◽  
Liviu Gabriel Bodea ◽  
Jürgen Götz
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Ribosomal Protein ◽  
Ribosomal Protein Synthesis ◽  
Noncanonical Amino Acid

scholarly journals A Potential Role for Aminoacylation in Primordial RNA Copying Chemistry

2020 ◽  
Author(s):  
Aleksandar Radakovic ◽  
Tom H. Wright ◽  
Victor S. Lelyveld ◽  
Jack W. Szostak
Keyword(s):  
Protein Synthesis ◽  
Fatty Acid ◽  
Amino Acid ◽  
Ribosomal Protein ◽  
Potential Role ◽  
Rna Replication ◽  
Primer Extension ◽  
Functional Link ◽  
Low Magnesium ◽  
Ribosomal Protein Synthesis

ABSTRACTAminoacylated tRNAs are the substrates for ribosomal protein synthesis in all branches of life, implying an ancient origin for aminoacylation chemistry. In the 1970s, Orgel and colleagues reported potentially prebiotic routes to aminoacylated nucleotides and their RNA templated condensation to form amino acid bridged dinucleotides. However, it is unclear whether such reactions would have aided or impeded nonenzymatic RNA replication. Determining whether aminoacylated RNAs could have been advantageous in evolution prior to the emergence of protein synthesis remains a key challenge. We therefore tested the ability of aminoacylated RNA to participate in both templated primer extension and ligation reactions. We find that at low magnesium concentrations that favor fatty acid-based protocells, these reactions proceed orders of magnitude more rapidly than when initiated from the cis-diol of unmodified RNA. We further demonstrate that amino acid bridged RNAs can act as templates in a subsequent round of copying. Our results suggest that aminoacylation facilitated nonenzymatic RNA replication, thus outlining a potentially primordial functional link between aminoacylation chemistry and RNA replication.Abstract Figure

scholarly journals The Reverse Side of a Coin: “Factor-Free” Ribosomal Protein Synthesis In Vitro is a Consequence of the In Vivo Proofreading Mechanism

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 588
Author(s):  
Finkelstein
Keyword(s):  
Quality Control ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Ribosomal Protein ◽  
Elongation Factor ◽  
Ribosomal Protein Synthesis

This paper elucidates a close connection between two well-known facts that until now have seemed independent: (i) the quality control (“proofreading”) of the emerging amino acid sequence, occurring during the normal, elongation-factor-dependent ribosomal biosynthesis, which is performed by removing those Aa-tRNAs (aminoacyl tRNAs) whose anticodons are not complementary to the exhibited mRNA codons, and (ii) the in vitro discovered existence of the factor-free ribosomal synthesis of polypeptides. It is shown that a biological role of proofreading is played by a process that is exactly opposite to the step of factor-free binding of Aa-tRNA to the ribosome-exposed mRNA: a factor-free removal of that Aa-tRNA whose anticodon is not complementary to the ribosome-exhibited mRNA codon.

scholarly journals The Origin of Prebiotic Information System in the Peptide/RNA World: A Simulation Model of the Evolution of Translation and the Genetic Code

Life ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 25 ◽  
Author(s):  
Sankar Chatterjee ◽  
Surya Yadav
Keyword(s):  
Amino Acids ◽  
Information System ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Genetic Code ◽  
Rna World ◽  
Trna Synthetase ◽  
Darwinian Evolution ◽  
Universal Genetic Code ◽  
Translation Machine

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital, and it appeared before the emergence of DNA. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and peptide molecules, which are drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: transfer RNAs (tRNAs), aminoacyl-tRNA synthetase (aaRS), messenger RNAs (mRNAs), ribosomes, and various enzymes. When assembled in the right order, the translation machine created proteins, a process that transferred information from mRNAs to assemble amino acids into polypeptide chains. This was the beginning of the prebiotic <i>information</i> age. The origin of the genetic code is enigmatic; herein, we propose an evolutionary explanation: the demand for a wide range of protein enzymes over peptides in the prebiotic reactions was the main selective pressure for the origin of information-directed protein synthesis. The molecular basis of the genetic code manifests itself in the interaction of aaRS and their cognate tRNAs. In the beginning, aminoacylated ribozymes used amino acids as a cofactor with the help of bridge peptides as a process for selection between amino acids and their cognate codons/anticodons. This process selects amino acids and RNA species for the next steps. The ribozymes would give rise to pre-tRNA and the bridge peptides to pre-aaRS. Later, variants would appear and evolution would produce different but specific aaRS-tRNA-amino acid combinations. Pre-tRNA designed and built pre-mRNA for the storage of information regarding its cognate amino acid. Each pre-mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within pre-mRNA and mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional with the emergence of the translation and genetic code. The genetic code developed in three stages that are coincident with the refinement of the translation machines: the GNC code that was developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. We suggest the coevolution of translation machines and the genetic code. The emergence of the translation machines was the beginning of the Darwinian evolution, an interplay between information and its supporting structure. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to better understand the prebiotic information system, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software, called CATI (Codon-Amino Acid-Translator-Imitator), to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the genetic code might have evolved in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics, such as barcoding, DNA mining, or DNA fingerprinting. We constructed 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. While using AnyLogic software, we were able to simulate and visualize the entire evolution of the translation machines, amino acids, and the genetic code.

Faster ribosome synthesis induced by elevated aortic pressure in rat heart

1987 ◽  
Vol 252 (3) ◽  
pp. C323-C327 ◽  
Author(s):  
B. H. Chua ◽  
L. A. Russo ◽  
E. E. Gordon ◽  
B. J. Kleinhans ◽  
H. E. Morgan
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Total Protein ◽  
Rat Heart ◽  
Relative Rate ◽  
Plasma Concentrations ◽  
Aortic Pressure ◽  
Rat Hearts ◽  
Ribosomal Protein Synthesis

An increase in aortic pressure from 60 to 120 mmHg accelerated ribosomal protein synthesis in rat hearts during 1 or 2 h of labeling with 0.4 mM [3H]phenylalanine. When hearts were perfused with buffer that contained 20 mM glucose and normal plasma concentrations of 19 other amino acids without added insulin, ribosomal protein synthesis relative to the rate of total protein synthesis increased from approximately 0.22 to 0.36 and 0.30 as aortic pressure was raised from 60 to 120 mmHg during 1 or 2 h of labeling, respectively. With the addition of insulin, the relative rate of ribosomal protein synthesis averaged 0.33 at an aortic pressure of 60 mmHg and increased to 0.42 when aortic pressure was raised to 120 mmHg. These results indicate that elevation of aortic pressure has a preferential effect on synthesis of new ribosomes. This response appears to be an early and physiologically significant event in cardiac hypertrophy.

scholarly journals The Origin of Prebiotic Information System in the Peptide/RNA World: A Simulation Model of the Evolution of Translation and the Genetic Code

2018 ◽  
Author(s):  
Sankar Chatterjee ◽  
Surya Yadav
Keyword(s):  
Amino Acids ◽  
Information System ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Genetic Code ◽  
Rna World ◽  
Information Age ◽  
Universal Genetic Code ◽  
Wide Range ◽  
Translation Machine

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital and probably appeared during biogenesis four billion years ago. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and protein molecules, drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: tRNAs, aaRS, mRNAs, and ribosomes. When assembled in the right order, the translation machine created biosynthetic polypeptides, a process that transferred information from mRNAs to proteins. This was the beginning of the prebiotic information age. The molecular attraction between tRNA and amino acids led to different stages of the translation machines and the genetic code. tRNA is an ancient molecule that designed and built mRNA for storing the information of its cognate amino acid. Each mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional. The origin of the genetic code is enigmatic; herein we propose an evolutionary explanation: the demand for a wide range of specific enzymes in the peptide/RNA world was the main selective pressure for the origin of information-directed protein synthesis. We review three main concepts on the origin and evolution of the genetic code: the stereochemical theory, the coevolution theory, and the adaptive theory. These three theories are compatible with our coevolution model of the translation machines and the genetic code. We suggest biosynthetic pathways as the origin of the specific translation machines which 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 machines: GNC code developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to understand the prebiotic information system better, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software called CATI (Codon-Amino Acid-Translator-Imitator) to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the translation might have worked in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics such as barcoding, DNA mining, or DNA fingerprinting. We constructed 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. Using AnyLogic software we were able to simulate and visualize the entire evolution of the translation machines and the genetic code. The results indicate that the emergence of the information age from the peptide/RNA world was a watershed event in the origin of life about four billion years ago.

scholarly journals Precocious germination and its regulation in embryos of triticale caryopses

2014 ◽  
Vol 56 (3) ◽  
pp. 469-483 ◽  
Author(s):  
Stanisław Weidner
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Ribosomal Proteins ◽  
Control Sample ◽  
Precocious Germination ◽  
Mature Embryos ◽  
Triticale Caryopses ◽  
Ribosomal Protein Synthesis ◽  
Stimulation Of

Triticale var. Lasko embryos, isolated from grain gathered at milk ripeness, the beginning of wax ripeness and at full ripeness, were allowed to germinate for 48 h on agar with glucose. The highest incorporation of tritiated adenosine into polyribosomal RNA during germination was found in the ribosome fractions from embryos of grain gathered at full ripeness, lower incorporation was in preparations from embryos of milk ripe grain and the lowest in preparations from embryos of wax ripe grain. Different tendencies were observed in respect to the synthesis of ribosomal proteins. The highest incorporation of <sup>14</sup>C-amino acids into ribosomal proteins was found in preparations of ribosome fractions from embryos of milk ripe grain, lower in preparations of embryos from fully ripe grain, the lowest in preparations of embryos from wax ripe grain. ABA (10<sup>-4</sup> M) completely inhibited the external symptoms of germination of immature embryos, while its inhibition of the synthesis of polyribosomal RNA and ribosomal proteins was greater the more mature the embryos that were germinated. The greatest stimulation of precocious germination by exogenous BA and GA<sub>3</sub> was demonstrated in the least mature embryos isolated from milk ripe grain. Under the influence of both stimulators, an increase of the proportion of polyribosomes in the total ribosome fraction occurred in this sample, as did a rise in the intensity of ribosomal protein synthesis. The incorporation of <sup>3</sup>H-adenosine into polyribosomal RNA, however, was lower than in the control sample. The results obtained suggest that the regulation of precocious germination of triticale embryos by phyto-hormones is not directly related to transcription.

scholarly journals 146 Prematurity Blunts the Protein Synthetic Response of Skeletal Muscle to Insulin and Amino Acids

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 118-119
Author(s):  
Teresa A Davis ◽  
Marko Rudar ◽  
Jane Naberhuis ◽  
Agus Suryawan ◽  
Marta Fiorotto
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Body Weight Gain ◽  
Human Infant ◽  
Long Term Effects ◽  
Plasma Insulin Concentration ◽  
Akt Phosphorylation ◽  
Relative Body Weight

Abstract Livestock animals are important dual-purpose models that benefit both agricultural and biomedical research. The neonatal pig is an appropriate model for the human infant to assess long-term effects of early life nutrition on growth and metabolic outcomes. Previously we have demonstrated that prematurity blunts the feeding-induced stimulation of translation initiation and protein synthesis in skeletal muscle of neonatal pigs. The objective of this study was to determine whether reduced sensitivity to insulin and/or amino acids drives this blunted response. Pigs were delivered by caesarean section at preterm (PT, 103 d gestation) or at term (T, 112 d gestation) and fed parenterally for 4 d. On day 4, pigs were subject to euinsulinemic-euaminoacidemic-euglycemic (FAST), hyperinsulinemic-euaminoacidemic-euglycemic (INS), or euinsulinemic-hyperaminoacidemic-euglycemic (AA) clamps for 120 min, yielding six treatments: PT-FAST (n = 7), PT-INS (n = 9), PT-AA (n = 9), T-FAST (n = 8), T-INS (n = 9), and T-AA (n = 9). A flooding dose of L-[4-3H]Phe was injected into pigs 30 min before euthanasia. Birth weight and relative body weight gain were lower in PT than T pigs (P &lt; 0.001). Plasma insulin concentration was increased from ~3 to ~100 µU/mL in INS compared to FAST and AA pigs (P &lt; 0.001); plasma BCAA concentration was increased from ~250 to ~1,000 µmol/L in AA compared to FAST and INS pigs (P &lt; 0.001). Despite achieving similar insulin and amino acid levels, longissimus dorsi AKT phosphorylation, mechanistic target of rapamycin (mTOR)·Rheb abundance, mTOR activation, and protein synthesis were lower in PT-INS than T-INS pigs (Table 1). Although amino-acid induced dissociation of Sestrin2 from GATOR2 was not affected by prematurity, mTOR·RagA abundance, mTOR·RagC abundance, mTOR activation, and protein synthesis were lower in PT-AA than T-AA pigs. The impaired capacity of premature skeletal muscle to respond to insulin or amino acids and promote protein synthesis likely contributes to reduced lean mass accretion. Research was supported by NIH and USDA.

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