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The Journal of Biological Chemistry Nov 2015Emerging evidence indicates that protein synthesis and degradation are necessary for the remodeling of synapses. These two processes govern cellular protein turnover,... (Review)
Review
Emerging evidence indicates that protein synthesis and degradation are necessary for the remodeling of synapses. These two processes govern cellular protein turnover, are tightly regulated, and are modulated by neuronal activity in time and space. The anisotropic anatomy of the neurons presents a challenge for the study of protein turnover, but the understanding of protein turnover in neurons and its modulation in response to activity can help us to unravel the fine-tuned changes that occur at synapses in response to activity. Here we review the key experimental evidence demonstrating the role of protein synthesis and degradation in synaptic plasticity, as well as the turnover rates of specific neuronal proteins.
Topics: Animals; Humans; Nerve Tissue Proteins; Neurons; Protein Biosynthesis; Proteolysis; Synapses
PubMed: 26453306
DOI: 10.1074/jbc.R115.657130 -
Antimicrobial Agents and Chemotherapy Apr 2017Antimicrobial peptides (AMPs) are expressed in various living organisms as first-line host defenses against potential harmful encounters in their surroundings. AMPs are... (Review)
Review
Antimicrobial peptides (AMPs) are expressed in various living organisms as first-line host defenses against potential harmful encounters in their surroundings. AMPs are short polycationic peptides exhibiting various antimicrobial activities. The principal antibacterial activity is attributed to the membrane-lytic mechanism which directly interferes with the integrity of the bacterial cell membrane and cell wall. In addition, a number of AMPs form a transmembrane channel in the membrane by self-aggregation or polymerization, leading to cytoplasm leakage and cell death. However, an increasing body of evidence has demonstrated that AMPs are able to exert intracellular inhibitory activities as the primary or supportive mechanisms to achieve efficient killing. In this review, we focus on the major intracellular targeting activities reported in AMPs, which include nucleic acids and protein biosynthesis and protein-folding, protease, cell division, cell wall biosynthesis, and lipopolysaccharide inhibition. These multifunctional AMPs could serve as the potential lead peptides for the future development of novel antibacterial agents with improved therapeutic profiles.
Topics: Anti-Infective Agents; Antimicrobial Cationic Peptides; Cell Membrane; Cell Wall; Microbial Sensitivity Tests; Protein Biosynthesis; Protein Folding
PubMed: 28167546
DOI: 10.1128/AAC.02340-16 -
International Journal of Molecular... Jan 2020Before utilization in biomedical diagnosis, therapeutic treatment, and biotechnology, the diverse variety of peptides and proteins must be preliminarily purified and... (Review)
Review
Before utilization in biomedical diagnosis, therapeutic treatment, and biotechnology, the diverse variety of peptides and proteins must be preliminarily purified and thoroughly characterized. The recombinant DNA technology and heterologous protein expression have helped simplify the isolation of targeted polypeptides at high purity and their structure-function examinations. Recombinant protein expression in , the most-established heterologous host organism, has been widely used to produce proteins of commercial and fundamental research interests. Nonetheless, many peptides/proteins are still difficult to express due to their ability to slow down cell growth or disrupt cellular metabolism. Besides, special modifications are often required for proper folding and activity of targeted proteins. The cell-free (CF) or in vitro recombinant protein synthesis system enables the production of such difficult-to-obtain molecules since it is possible to adjust reaction medium and there is no need to support cellular metabolism and viability. Here, we describe -based CF systems, the optimization steps done toward the development of highly productive and cost-effective CF methodology, and the modification of an in vitro approach required for difficult-to-obtain protein production.
Topics: Cell-Free System; Escherichia coli; Protein Biosynthesis; Protein Engineering; Protein Processing, Post-Translational; Recombinant Proteins
PubMed: 32023820
DOI: 10.3390/ijms21030928 -
Cold Spring Harbor Perspectives in... Nov 2018One of the last hurdles to quantifying the full central dogma of molecular biology in living cells with single-molecule resolution has been the imaging of single... (Review)
Review
One of the last hurdles to quantifying the full central dogma of molecular biology in living cells with single-molecule resolution has been the imaging of single messenger RNA (mRNA) translation. Here we describe how recent advances in protein tagging and imaging technologies are being used to precisely visualize and quantify the synthesis of nascent polypeptide chains from single mRNA in living cells. We focus on recent applications of repeat-epitope tags and describe how they enable quantification of single mRNA ribosomal densities, translation initiation and elongation rates, and translation site mobility and higher-order structure. Together with complementary live-cell assays to monitor translation using fast-maturing fluorophores and mRNA-binding protein knockoff, single-molecule studies are beginning to uncover striking and unexpected heterogeneity in gene expression at the level of translation.
Topics: Epitopes; Gene Expression Regulation; Humans; Molecular Imaging; Peptide Chain Elongation, Translational; Protein Biosynthesis; RNA, Messenger
PubMed: 30385605
DOI: 10.1101/cshperspect.a032078 -
Cold Spring Harbor Perspectives in... Nov 2018A growing collection of bacterial riboswitch classes is being discovered that sense central metabolites, coenzymes, and signaling molecules. Included among the various... (Review)
Review
A growing collection of bacterial riboswitch classes is being discovered that sense central metabolites, coenzymes, and signaling molecules. Included among the various mechanisms of gene regulation exploited by these RNA regulatory elements are several that modulate messenger RNA (mRNA) translation. In this review, the mechanisms of riboswitch-mediated translation control are summarized to highlight both their diversity and potential ancient origins. These mechanisms include ligand-gated presentation or occlusion of ribosome-binding sites, control of alternative splicing of mRNAs, and the regulation of mRNA stability. Moreover, speculation on the potential for novel riboswitch discoveries is presented, including a discussion on the potential for the discovery of a greater diversity of mechanisms for translation control.
Topics: Animals; Gene Expression Regulation; Protein Biosynthesis; RNA Splicing; Riboswitch
PubMed: 29844057
DOI: 10.1101/cshperspect.a032797 -
The Journal of Biological Chemistry Jul 2020Bacteria must rapidly respond to both intracellular and environmental changes to survive. One critical mechanism to rapidly detect and adapt to changes in environmental... (Review)
Review
Bacteria must rapidly respond to both intracellular and environmental changes to survive. One critical mechanism to rapidly detect and adapt to changes in environmental conditions is control of gene expression at the level of protein synthesis. At each of the three major steps of translation-initiation, elongation, and termination-cells use stimuli to tune translation rate and cellular protein concentrations. For example, changes in nutrient concentrations in the cell can lead to translational responses involving mechanisms such as dynamic folding of riboswitches during translation initiation or the synthesis of alarmones, which drastically alter cell physiology. Moreover, the cell can fine-tune the levels of specific protein products using programmed ribosome pausing or inducing frameshifting. Recent studies have improved understanding and revealed greater complexity regarding long-standing paradigms describing key regulatory steps of translation such as start-site selection and the coupling of transcription and translation. In this review, we describe how bacteria regulate their gene expression at the three translational steps and discuss how translation is used to detect and respond to changes in the cellular environment. Finally, we appraise the costs and benefits of regulation at the translational level in bacteria.
Topics: Adaptation, Physiological; Bacteria; Bacterial Proteins; Protein Biosynthesis
PubMed: 32518156
DOI: 10.1074/jbc.REV120.012742 -
The Journal of Biological Chemistry Aug 2023The notion that errors in protein synthesis are universally harmful to the cell has been questioned by findings that suggest such mistakes may sometimes be beneficial....
The notion that errors in protein synthesis are universally harmful to the cell has been questioned by findings that suggest such mistakes may sometimes be beneficial. However, how often these beneficial mistakes arise from programmed changes in gene expression as opposed to reduced accuracy of the translation machinery is still unclear. A new study published in JBC shows that some bacteria have beneficially evolved the ability to mistranslate specific parts of the genetic code, a trait that allows improved antibiotic resistance.
Topics: Bacteria; Genetic Code; Protein Biosynthesis; RNA, Transfer
PubMed: 37380073
DOI: 10.1016/j.jbc.2023.104974 -
Results and Problems in Cell... 2017Germline poses unique challenges to gene expression control at the transcriptional level. While the embryonic germline maintains a global hold on new mRNA transcription,... (Review)
Review
Germline poses unique challenges to gene expression control at the transcriptional level. While the embryonic germline maintains a global hold on new mRNA transcription, the female adult germline produces transcripts that are not translated into proteins until embryogenesis of subsequent generation. As a consequence, translational control plays a central role in governing various germ cell decisions including the formation of primordial germ cells, self-renewal/differentiation decisions in the adult germline, onset of gametogenesis and oocyte maturation. Mechanistically, several common themes such as asymmetric localization of mRNAs, conserved RNA-binding proteins that control translation by 3' UTR binding, translational activation by the cytoplasmic elongation of the polyA tail and the assembly of mRNA-protein complexes called mRNPs have emerged from the studies on Caenorhabditis elegans, Xenopus and Drosophila. How mRNPs assemble, what influences their dynamics, and how a particular 3' UTR-binding protein turns on the translation of certain mRNAs while turning off other mRNAs at the same time and space are key challenges for future work.
Topics: Animals; Female; Gene Expression Regulation; Germ Cells; Humans; Male; Protein Biosynthesis
PubMed: 28247049
DOI: 10.1007/978-3-319-44820-6_6 -
Amino Acids Dec 2021Proline is a non-essential amino acid with key roles in protein structure/function and maintenance of cellular redox homeostasis. It is available from dietary sources,... (Review)
Review
Proline is a non-essential amino acid with key roles in protein structure/function and maintenance of cellular redox homeostasis. It is available from dietary sources, generated de novo within cells, and released from protein structures; a noteworthy source being collagen. Its catabolism within cells can generate ATP and reactive oxygen species (ROS). Recent findings suggest that proline biosynthesis and catabolism are essential processes in disease; not only due to the role in new protein synthesis as part of pathogenic processes but also due to the impact of proline metabolism on the wider metabolic network through its significant role in redox homeostasis. This is particularly clear in cancer proliferation and metastatic outgrowth. Nevertheless, the precise identity of the drivers of cellular proline catabolism and biosynthesis, and the overall cost of maintaining appropriate balance is not currently known. In this review, we explore the major drivers of proline availability and consumption at a local and systemic level with a focus on cancer. Unraveling the main factors influencing proline metabolism in normal physiology and disease will shed light on new effective treatment strategies.
Topics: Animals; Homeostasis; Humans; Neoplasms; Oxidation-Reduction; Proline; Protein Biosynthesis; Reactive Oxygen Species
PubMed: 34291343
DOI: 10.1007/s00726-021-03051-2 -
The Journal of General Physiology Jul 1966Outline of the steps in protein synthesis. Nature of the genetic code. The use of synthetic oligo- and polynucleotides in deciphering the code. Structure of the code:... (Review)
Review
Outline of the steps in protein synthesis. Nature of the genetic code. The use of synthetic oligo- and polynucleotides in deciphering the code. Structure of the code: relatedness of synonym codons. The wobble hypothesis. Chain initiation and N-formyl-methionine. Chain termination and nonsense codons. Mistakes in translation: ambiguity in vitro. Suppressor mutations resulting in ambiguity. Limitations in the universality of the code. Attempts to determine the particular codons used by a species. Mechanisms of suppression, caused by (a) abnormal aminoacyl-tRNA, (b) ribosomal malfunction. Effect of streptomycin. The problem of "reading" a nucleic acid template. Different ribosomal mutants and DNA polymerase mutants might cause different mistakes. The possibility of involvement of allosteric proteins in template reading.
Topics: Genetic Code; Protein Biosynthesis
PubMed: 5338560
DOI: 10.1085/jgp.49.6.305