-
Biochemistry Mar 2019
Review
Topics: Acetylation; Cytidine; Humans; Protein Biosynthesis; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Messenger
PubMed: 30875197
DOI: 10.1021/acs.biochem.9b00061 -
Biochemical Society Transactions Feb 2019The expression level of a gene can fluctuate significantly between individuals within a population of genetically identical cells. The resultant phenotypic heterogeneity... (Review)
Review
The expression level of a gene can fluctuate significantly between individuals within a population of genetically identical cells. The resultant phenotypic heterogeneity could be exploited by bacteria to adapt to changing environmental conditions. Noise is hence a genome-wide phenomenon that arises from the stochastic nature of the biochemical reactions that take place during gene expression and the relatively low abundance of the molecules involved. The production of mRNA and proteins therefore occurs in bursts, with alternating episodes of high and low activity during transcription and translation. Single-cell and single-molecule studies demonstrated that noise within gene expression is influenced by a combination of both intrinsic and extrinsic factors. However, our mechanistic understanding of this process at the molecular level is still rather limited. Further investigation is necessary that takes into account the detailed knowledge of gene regulation gained from biochemical studies.
Topics: Bacteria; Genes, Bacterial; Protein Biosynthesis; RNA, Messenger; Transcription, Genetic
PubMed: 30578346
DOI: 10.1042/BST20180500 -
Open Biology Jul 2019Many antibiotics available in the clinic today directly inhibit bacterial translation. Despite the past success of such drugs, their efficacy is diminishing with the... (Review)
Review
Many antibiotics available in the clinic today directly inhibit bacterial translation. Despite the past success of such drugs, their efficacy is diminishing with the spread of antibiotic resistance. Through the use of ribosomal modifications, ribosomal protection proteins, translation elongation factors and mistranslation, many pathogens are able to establish resistance to common therapeutics. However, current efforts in drug discovery are focused on overcoming these obstacles through the modification or discovery of new treatment options. Here, we provide an overview for common mechanisms of resistance to translation-targeting drugs and summarize several important breakthroughs in recent drug development.
Topics: Animals; Anti-Bacterial Agents; Drug Discovery; Drug Resistance, Bacterial; Humans; Molecular Targeted Therapy; Protein Biosynthesis; Protein Processing, Post-Translational; Ribosomal Proteins; Ribosomes
PubMed: 31288624
DOI: 10.1098/rsob.190051 -
Ageing Research Reviews Sep 2015Ageing is manifested as functional and structural deterioration that affects cell and tissue physiology. mRNA translation is a central cellular process, supplying cells... (Review)
Review
Ageing is manifested as functional and structural deterioration that affects cell and tissue physiology. mRNA translation is a central cellular process, supplying cells with newly synthesized proteins. Accumulating evidence suggests that alterations in protein synthesis are not merely a corollary but rather a critical factor for the progression of ageing. Here, we survey protein synthesis regulatory mechanisms and focus on the pre-translational regulation of the process exerted by non-coding RNA species, RNA binding proteins and alterations of intrinsic RNA properties. In addition, we discuss the tight relationship between mRNA translation and two central pathways that modulate ageing, namely the insulin/IGF-1 and TOR signalling cascades. A thorough understanding of the complex interplay between protein synthesis regulation and ageing will provide critical insights into the pathogenesis of age-related disorders, associated with impaired proteostasis and protein quality control.
Topics: Aging; Animals; Humans; Protein Biosynthesis; Quality Control; RNA Processing, Post-Transcriptional; RNA, Untranslated; RNA-Binding Proteins
PubMed: 25555680
DOI: 10.1016/j.arr.2014.12.008 -
Proteomics Oct 2015
Topics: Gene Expression; Humans; Microbiota; Protein Biosynthesis; Proteomics
PubMed: 26468045
DOI: 10.1002/pmic.201570183 -
Clinical Nutrition (Edinburgh, Scotland) Apr 2021Muscle protein synthesis (MPS) is a complex and finely-regulated mechanism that plays a key role in muscle homeostasis. Amino acid bioavailability is widely considered a... (Review)
Review
Muscle protein synthesis (MPS) is a complex and finely-regulated mechanism that plays a key role in muscle homeostasis. Amino acid bioavailability is widely considered a major driver of MPS regulation via mTOR pathway activation. However, recent results suggest that amino acid bioavailability affects cellular energy status. Whatever the tool used to modulate energy status (amino acid depletion or mild mitochondrial uncoupling), a decrease in cellular energy status decreases MPS, without necessarily involving the mTOR pathway. Here we propose that energy status directly regulates one or several energy-consuming step(s) during MPS. This new paradigm modifies our vision of protein metabolism and raises prospects for new advances in therapeutics.
Topics: Energy Metabolism; Humans; Muscle Proteins; Protein Biosynthesis
PubMed: 32788089
DOI: 10.1016/j.clnu.2020.07.015 -
Cold Spring Harbor Perspectives in... Jun 2018The ability to block biological processes with selective small molecules provides advantages distinct from most other experimental approaches. These include rapid time... (Review)
Review
The ability to block biological processes with selective small molecules provides advantages distinct from most other experimental approaches. These include rapid time to onset, swift reversibility, ability to probe activities in manners that cannot be accessed by genetic means, and the potential to be further developed as therapeutic agents. Small molecule inhibitors can also be used to alter expression and activity without affecting the stoichiometry of interacting partners. These tenets have been especially evident in the field of translation. Small molecule inhibitors were instrumental in enabling investigators to capture short-lived complexes and characterize specific steps of protein synthesis. In addition, several drugs that are the mainstay of modern antimicrobial drug therapy are potent inhibitors of prokaryotic translation. Currently, there is much interest in targeting eukaryotic translation as decades of research have revealed that deregulated protein synthesis in cancer cells represents a targetable vulnerability. In addition to being potential therapeutics, small molecules that manipulate translation have also been shown to influence cognitive processes such as memory. In this review, we focus on small molecule modulators that target the eukaryotic translation initiation apparatus and provide an update on their potential application to the treatment of disease.
Topics: Animals; Antineoplastic Agents; Gene Expression Regulation, Neoplastic; Protein Biosynthesis
PubMed: 29440069
DOI: 10.1101/cshperspect.a032995 -
Progress in Biophysics and Molecular... 1971
Review
Topics: Amino Acid Sequence; Binding Sites; Chemical Phenomena; Chemistry, Physical; Chromatin; Chromosomes; Circular Dichroism; Coliphages; DNA; Enzyme Repression; Genes, Regulator; Macromolecular Substances; Nucleoproteins; Optical Rotatory Dispersion; Peptide Chain Elongation, Translational; Peptide Chain Initiation, Translational; Peptide Chain Termination, Translational; Protein Binding; Protein Biosynthesis; Proteins; RNA; RNA Nucleotidyltransferases; Ribosomes; Viruses; X-Ray Diffraction
PubMed: 4946428
DOI: 10.1016/0079-6107(71)90018-6 -
Biochemistry Aug 2019
Topics: Protein Biosynthesis; Protein Engineering; Proteins
PubMed: 31343161
DOI: 10.1021/acs.biochem.9b00569 -
Cell Systems Sep 2017Protein turnover maintains the recycling needs of the proteome, and its malfunction has been linked to aging and age-related diseases. However, not all proteins...
Protein turnover maintains the recycling needs of the proteome, and its malfunction has been linked to aging and age-related diseases. However, not all proteins turnover equally, and the factors that contribute to accelerate or slow down turnover are mostly unknown. We measured turnover rates for 3,160 proteins in exponentially growing yeast and analyzed their dependence on physical, functional, and genetic properties. We found that functional characteristics, including protein localization, complex membership, and connectivity, have greater effect on turnover than sequence elements. We also found that protein turnover and mRNA turnover are correlated. Analysis under nutrient perturbation and osmotic stress revealed that protein turnover highly depends on cellular state and is faster when proteins are being actively used. Finally, stress-induced changes in protein and transcript abundance correlated with changes in protein turnover. This study provides a resource of protein turnover rates and principles to understand the recycling needs of the proteome under basal conditions and perturbation.
Topics: Half-Life; Osmotic Pressure; Protein Biosynthesis; Protein Stability; Proteins; Proteolysis; Proteome; Proteomics; RNA Stability; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 28918244
DOI: 10.1016/j.cels.2017.08.008