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Current Opinion in Plant Biology Oct 2023Transposons are mobile DNA sequences that can move within the genome and integrate in new genomic locations. They are widespread in eukaryotes and prokaryotes and can... (Review)
Review
Transposons are mobile DNA sequences that can move within the genome and integrate in new genomic locations. They are widespread in eukaryotes and prokaryotes and can influence gene expression when landing within or nearby a gene. Although transposon-induced regulation of gene expression at the transcriptional level has been extensively studied, there has been less focus on regulation at the post-transcriptional and translational levels. Recent studies in maize (Zea mays) and other plant species suggest that transposon insertions can affect RNA processing, RNA stability, protein translation and protein stability. We will describe the diverse mechanisms by which transposons can influence gene expression at the post-transcriptional and translational levels, and discuss the interactions between these mechanisms.
Topics: Genes, Plant; Genomics; Protein Biosynthesis; RNA Stability; Zea mays
PubMed: 37619514
DOI: 10.1016/j.pbi.2023.102438 -
Current Opinion in Microbiology Feb 2024Sensing small molecules is crucial for microorganisms to adapt their genetic programs to changes in their environment. Arrest peptides encoded by short regulatory... (Review)
Review
Sensing small molecules is crucial for microorganisms to adapt their genetic programs to changes in their environment. Arrest peptides encoded by short regulatory open reading frames program the ribosomes that translate them to undergo translational arrest in response to specific metabolites. Ribosome stalling in turn controls the expression of downstream genes on the same messenger RNA by translational or transcriptional means. In this review, we present our current understanding of the mechanisms by which ribosomes translating arrest peptides sense different metabolites, such as antibiotics or amino acids, to control gene expression.
Topics: Protein Biosynthesis; Ribosomes; Peptides; Anti-Bacterial Agents
PubMed: 38159358
DOI: 10.1016/j.mib.2023.102418 -
Infection and Immunity Oct 2023Bacteria frequently interfere with the post-translational modifications of host cells to facilitate their survival and growth after invasion. SUMOylation, a reversible... (Review)
Review
Bacteria frequently interfere with the post-translational modifications of host cells to facilitate their survival and growth after invasion. SUMOylation, a reversible post-translational modification process, plays an important role in biological life activities. In addition to being critical to host cell metabolism and survival, SUMOylation also regulates gene expression and cell signal transmission. Moreover, SUMOylation in eukaryotic cells can be used by a variety of bacterial pathogens to advance bacterial invasion. In this minireview, we focused on the role and mechanism of host SUMOylation in the pathogenesis of six important clinical bacterial pathogens (, , Typhimurium, , and ). Taken together, this review provided new insights for understanding the unique pathogen-host interaction based on host SUMOylation and provided a novel perspective on the development of new strategies to combat bacterial infections in the future.
Topics: Humans; Sumoylation; Bacterial Infections; Listeria monocytogenes; Protein Processing, Post-Translational; Salmonella typhimurium
PubMed: 37725062
DOI: 10.1128/iai.00283-23 -
Applied Microbiology and Biotechnology Feb 2024Terpenoids are a class of structurally complex, naturally occurring compounds found predominantly in plant, animal, and microorganism secondary metabolites. Classical... (Review)
Review
Terpenoids are a class of structurally complex, naturally occurring compounds found predominantly in plant, animal, and microorganism secondary metabolites. Classical terpenoids typically have carbon atoms in multiples of five and follow well-defined carbon skeletons, whereas noncanonical terpenoids deviate from these patterns. These noncanonical terpenoids often result from the methyltransferase-catalyzed methylation modification of substrate units, leading to irregular carbon skeletons. In this comprehensive review, various activities and applications of these noncanonical terpenes have been summarized. Importantly, the review delves into the biosynthetic pathways of noncanonical terpenes, including those with C6, C7, C11, C12, and C16 carbon skeletons, in bacteria and fungi host. It also covers noncanonical triterpenes synthesized from non-squalene substrates and nortriterpenes in Ganoderma lucidum, providing detailed examples to elucidate the intricate biosynthetic processes involved. Finally, the review outlines the potential future applications of noncanonical terpenoids. In conclusion, the insights gathered from this review provide a reference for understanding the biosynthesis of these noncanonical terpenes and pave the way for the discovery of additional unique and novel noncanonical terpenes. KEY POINTS: •The activities and applications of noncanonical terpenoids are introduced. •The noncanonical terpenoids with irregular carbon skeletons are presented. •The microbial biosynthesis of noncanonical terpenoids is summarized.
Topics: Animals; Terpenes; Triterpenes; Carbon; Methyltransferases; Protein Processing, Post-Translational
PubMed: 38381229
DOI: 10.1007/s00253-024-13048-y -
Biomedicine & Pharmacotherapy =... Nov 2023Skeletal muscle, the largest organ in the human body, plays a crucial role in supporting and defending the body and is essential for movement. It also participates in... (Review)
Review
Skeletal muscle, the largest organ in the human body, plays a crucial role in supporting and defending the body and is essential for movement. It also participates in regulating the processes of protein synthesis and degradation. Inhibition of protein synthesis and activation of degradation metabolism can both lead to the development of skeletal muscle atrophy, a pathological condition characterized by a decrease in muscle mass and fiber size. Many physiological and pathological conditions can cause a decline in muscle mass, but the underlying mechanisms of its pathogenesis remain incompletely understood, and the selection of treatment strategies and efficacy evaluations vary. Moreover, the early symptoms of this condition are often not apparent, making it easily overlooked in clinical practice. Therefore, it is necessary to develop and use cell models to understand the etiology and influencing factors of skeletal muscle atrophy. In this review, we summarize the methods used to construct skeletal muscle cell models, including hormone, inflammation, cachexia, genetic engineering, drug, and physicochemical models. We also analyze, compare, and evaluate the various construction and assessment methods.
Topics: Humans; Muscular Atrophy; Muscle, Skeletal; Muscle Fibers, Skeletal; Cachexia; Protein Biosynthesis
PubMed: 37738794
DOI: 10.1016/j.biopha.2023.115517 -
The Journal of Cell Biology Jul 2024How nucleocytoplasmic transport (NCT) rates change due to cellular physiology-mediated fluctuations in GTP availability remains unclear. In this issue, Scott et al....
How nucleocytoplasmic transport (NCT) rates change due to cellular physiology-mediated fluctuations in GTP availability remains unclear. In this issue, Scott et al. (https://doi.org/10.1083/jcb.202308152) demonstrate that cell migration, spreading, and nucleocytoskeletal coupling impact GTP levels, thereby regulating NCT, RNA export, and protein synthesis.
Topics: Humans; Active Transport, Cell Nucleus; Cell Movement; Cell Nucleus; Energy Metabolism; Guanosine Triphosphate; Protein Biosynthesis
PubMed: 38847483
DOI: 10.1083/jcb.202405121 -
Acta Biochimica Et Biophysica Sinica Aug 2023Autophagy, an efficient and effective approach to clear rapidly damaged organelles, macromolecules, and other harmful cellular components, enables the recycling of...
Autophagy, an efficient and effective approach to clear rapidly damaged organelles, macromolecules, and other harmful cellular components, enables the recycling of nutrient materials and supply of nutrients to maintain cellular homeostasis. Ubiquitination plays an important regulatory role in autophagy. This paper summarizes the most recent progress in ubiquitin modification in various stages of autophagy, including initiation, elongation, and termination. Moreover, this paper shows that ubiquitination is an important way through which selective autophagy achieves substrate specificity. Furthermore, we note the distinction between monoubiquitination and polyubiquitination in the regulation of autophagy. Compared with monoubiquitination, polyubiquitination is a more common strategy to regulate the activity of the autophagy molecular machinery. In addition, the role of ubiquitination in the closure and fusion of autophagosomes warrants further study. This article not only clarifies the regulatory mechanism of autophagy but also contributes to a deeper understanding of the importance of ubiquitination modification.
Topics: Autophagy; Ubiquitination; Autophagosomes; Ubiquitin; Cognition
PubMed: 37587758
DOI: 10.3724/abbs.2023149 -
The Journal of Biological Chemistry Sep 2023Recent discoveries establish tRNAs as central regulators of mRNA translation dynamics, and therefore cotranslational folding and function of the encoded protein. The... (Review)
Review
Recent discoveries establish tRNAs as central regulators of mRNA translation dynamics, and therefore cotranslational folding and function of the encoded protein. The tRNA pool, whose composition and abundance change in a cell- and tissue-dependent manner, is the main factor which determines mRNA translation velocity. In this review, we discuss a group of pathogenic mutations, in the coding sequences of either protein-coding genes or in tRNA genes, that alter mRNA translation dynamics. We also summarize advances in tRNA biology that have uncovered how variations in tRNA levels on account of genetic mutations affect protein folding and function, and thereby contribute to phenotypic diversity in clinical manifestations.
Topics: Humans; Codon; Mutation; Protein Biosynthesis; RNA, Messenger; RNA, Transfer; Polymorphism, Single Nucleotide; Time Factors
PubMed: 37495112
DOI: 10.1016/j.jbc.2023.105089 -
Nature Chemical Biology Sep 2023The proline-rich antimicrobial peptide (PrAMP) Drosocin (Dro) from fruit flies shows sequence similarity to other PrAMPs that bind to the ribosome and inhibit protein...
The proline-rich antimicrobial peptide (PrAMP) Drosocin (Dro) from fruit flies shows sequence similarity to other PrAMPs that bind to the ribosome and inhibit protein synthesis by varying mechanisms. The target and mechanism of action of Dro, however, remain unknown. Here we show that Dro arrests ribosomes at stop codons, probably sequestering class 1 release factors associated with the ribosome. This mode of action is comparable to that of apidaecin (Api) from honeybees, making Dro the second member of the type II PrAMP class. Nonetheless, analysis of a comprehensive library of endogenously expressed Dro mutants shows that the interactions of Dro and Api with the target are markedly distinct. While only a few C-terminal amino acids of Api are critical for binding, the interaction of Dro with the ribosome relies on multiple amino acid residues distributed throughout the PrAMP. Single-residue substitutions can substantially enhance the on-target activity of Dro.
Topics: Animals; Antimicrobial Peptides; Escherichia coli; Glycopeptides; Protein Biosynthesis; Drosophila
PubMed: 36997647
DOI: 10.1038/s41589-023-01300-x -
Nature Communications May 2024Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with diverse chemical structures and potent biological...
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with diverse chemical structures and potent biological activities. A vast majority of RiPP gene clusters remain unexplored in microbial genomes, which is partially due to the lack of rapid and efficient heterologous expression systems for RiPP characterization and biosynthesis. Here, we report a unified biocatalysis (UniBioCat) system based on cell-free gene expression for rapid biosynthesis and engineering of RiPPs. We demonstrate UniBioCat by reconstituting a full biosynthetic pathway for de novo biosynthesis of salivaricin B, a lanthipeptide RiPP. Next, we delete several protease/peptidase genes from the source strain to enhance the performance of UniBioCat, which then can synthesize and screen salivaricin B variants with enhanced antimicrobial activity. Finally, we show that UniBioCat is generalizable by synthesizing and evaluating the bioactivity of ten uncharacterized lanthipeptides. We expect UniBioCat to accelerate the discovery, characterization, and synthesis of RiPPs.
Topics: Ribosomes; Cell-Free System; Protein Processing, Post-Translational; Peptides; Biosynthetic Pathways; Multigene Family; Biocatalysis
PubMed: 38773100
DOI: 10.1038/s41467-024-48726-y