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Brain Research Aug 2018RNA binding proteins play essential roles during development and aging, and are also involved in disease pathomechanisms. RNA sequencing and omics analyses have provided... (Review)
Review
RNA binding proteins play essential roles during development and aging, and are also involved in disease pathomechanisms. RNA sequencing and omics analyses have provided a window into systems level alterations in neurological disease, and have identified RNA processing defects among notable disease mechanisms. This review focuses on two seemingly distinct neurological disorders, the RNA binding proteins they are linked to, and their newly discovered functional relationship. When deficient, Fragile X Mental Retardation Protein (FMRP) causes developmental deficits and autistic behaviors while TAR-DNA Binding Protein (TDP-43) dysregulation causes age dependent neuronal degeneration. Recent findings that FMRP and TDP-43 associate in ribonuclear protein particles and share mRNA targets in neurons highlight the critical importance of translation regulation in synaptic plasticity and provide new perspectives on neuronal vulnerability during lifespan.
Topics: Animals; DNA-Binding Proteins; Disease Models, Animal; Fragile X Mental Retardation Protein; Fragile X Syndrome; Humans; Neuronal Plasticity; Neurons; Protein Biosynthesis; RNA, Messenger; Receptors, Metabotropic Glutamate; Ribonucleoproteins; Signal Transduction
PubMed: 29715444
DOI: 10.1016/j.brainres.2018.04.034 -
Cell Reports Jan 2016The economy of protein production is central to cell physiology, being intimately linked with cell division rate and cell size. Attempts to model cellular physiology are...
The economy of protein production is central to cell physiology, being intimately linked with cell division rate and cell size. Attempts to model cellular physiology are limited by the scarcity of experimental data defining the molecular processes limiting protein expression. Here, we distinguish the relative contribution of gene transcription and protein translation to the slower proliferation of budding yeast producing excess levels of unneeded proteins. In contrast to widely held assumptions, rapidly growing cells are not universally limited by ribosome content. Rather, transcription dominates cost under some conditions (e.g., low phosphate), translation in others (e.g., low nitrogen), and both in other conditions (e.g., rich media). Furthermore, cells adapted to enforced protein production by becoming larger and increasing their endogenous protein levels, suggesting limited competition for common resources. We propose that rapidly growing cells do not exhaust their resources to maximize growth but maintain sufficient reserves to accommodate changing requirements.
Topics: Gene Expression Regulation, Fungal; Protein Biosynthesis; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Transcription, Genetic
PubMed: 26725116
DOI: 10.1016/j.celrep.2015.12.015 -
Philosophical Transactions of the Royal... Mar 2017The basic steps of protein synthesis are carried out by the ribosome, a very large and complex ribonucleoprotein particle. In keeping with its proposed emergence from an... (Review)
Review
The basic steps of protein synthesis are carried out by the ribosome, a very large and complex ribonucleoprotein particle. In keeping with its proposed emergence from an RNA world, all three of its core mechanisms-aminoacyl-tRNA selection, catalysis of peptide bond formation and coupled translocation of mRNA and tRNA-are embodied in the properties of ribosomal RNA, while its proteins play a supportive role.This article is part of the themed issue 'Perspectives on the ribosome'.
Topics: Origin of Life; Protein Biosynthesis; RNA; Transfer RNA Aminoacylation; Translocation, Genetic
PubMed: 28138073
DOI: 10.1098/rstb.2016.0187 -
Cold Spring Harbor Perspectives in... Aug 2018In this review, we highlight the current understanding of translation elongation and recoding in eukaryotes. In addition to providing an overview of the process, recent... (Review)
Review
In this review, we highlight the current understanding of translation elongation and recoding in eukaryotes. In addition to providing an overview of the process, recent advances in our understanding of the role of the factor eIF5A in both translation elongation and termination are discussed. We also highlight mechanisms of translation recoding with a focus on ribosomal frameshifting during elongation. We see that the balance between the basic steps in elongation and the less common recoding events is determined by the kinetics of the different processes as well as by specific sequence determinants.
Topics: Eukaryota; Frameshifting, Ribosomal; Gene Expression Regulation; Protein Biosynthesis
PubMed: 29610120
DOI: 10.1101/cshperspect.a032649 -
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 -
The Journal of Nutrition Jan 2022
Topics: Amino Acids; Muscle Proteins; Muscles; Protein Biosynthesis
PubMed: 35021214
DOI: 10.1093/jn/nxab370 -
Proceedings of the National Academy of... Jul 2020Memory reconsolidation occurs when a retrieving event destabilizes transiently a consolidated memory, triggering thereby a new process of restabilization that ensures...
Memory reconsolidation occurs when a retrieving event destabilizes transiently a consolidated memory, triggering thereby a new process of restabilization that ensures memory persistence. Although this phenomenon has received wide attention, the effect of new information cooccurring with the reconsolidation process has been less explored. Here we demonstrate that a memory-retrieving event sets a neural tag, which enables the reconsolidation of memory after binding proteins provided by the original or a different contiguous experience. We characterized the specific temporal window during which this association is effective and identified the protein kinase A (PKA) and the extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathways as the mechanisms related to the setting of the reconsolidation tag and the synthesis of proteins. Our results show, therefore, that memory reconsolidation is mediated by a "behavioral tagging" process, which is common to different memory forms. They represent a significant advance in understanding the fate of memories reconsolidated while being adjacent to other events, and provide a tool for designing noninvasive strategies to attenuate (pathological/traumatic) or improve (education-related) memories.
Topics: Animals; Behavior; Biomarkers; Male; Memory; Memory Consolidation; Protein Biosynthesis; Protein Synthesis Inhibitors; Rats
PubMed: 32665437
DOI: 10.1073/pnas.2009517117 -
BMB Reports Jan 2020The mitochondrial genome encodes 13 proteins that are components of the oxidative phosphorylation system (OXPHOS), suggesting that precise regulation of these genes is... (Review)
Review
The mitochondrial genome encodes 13 proteins that are components of the oxidative phosphorylation system (OXPHOS), suggesting that precise regulation of these genes is crucial for maintaining OXPHOS functions, including ATP production, calcium buffering, cell signaling, ROS production, and apoptosis. Furthermore, heteroplasmy or mis-regulation of gene expression in mitochondria frequently is associated with human mitochondrial diseases. Thus, various approaches have been developed to investigate the roles of genes encoded by the mitochondrial genome. In this review, we will discuss a wide range of techniques available for investigating the mitochondrial genome, mitochondrial transcription, and mitochondrial translation, which provide a useful guide to understanding mitochondrial gene expression. [BMB Reports 2020; 53(1): 3-9].
Topics: Animals; Clustered Regularly Interspaced Short Palindromic Repeats; DNA, Mitochondrial; Humans; In Situ Hybridization, Fluorescence; MicroRNAs; Mitochondrial Proteins; Protein Biosynthesis; RNA, Mitochondrial; Transcription Activator-Like Effector Nucleases; Transcription, Genetic
PubMed: 31818361
DOI: 10.5483/BMBRep.2020.53.1.272 -
Toxins Apr 2019Ricin belongs to the group of ribosome-inactivating proteins (RIPs), i.e., toxins that have evolved to provide particular species with an advantage over other... (Review)
Review
Ricin belongs to the group of ribosome-inactivating proteins (RIPs), i.e., toxins that have evolved to provide particular species with an advantage over other competitors in nature. Ricin possesses RNA N-glycosidase activity enabling the toxin to eliminate a single adenine base from the sarcin-ricin RNA loop (SRL), which is a highly conserved structure present on the large ribosomal subunit in all species from the three domains of life. The SRL belongs to the GTPase associated center (GAC), i.e., a ribosomal element involved in conferring unidirectional trajectory for the translational apparatus at the expense of GTP hydrolysis by translational GTPases (trGTPases). The SRL represents a critical element in the GAC, being the main triggering factor of GTP hydrolysis by trGTPases. Enzymatic removal of a single adenine base at the tip of SRL by ricin blocks GTP hydrolysis and, at the same time, impedes functioning of the translational machinery. Here, we discuss the consequences of SRL depurination by ricin for ribosomal performance, with emphasis on the mechanistic model overview of the SRL .
Topics: Animals; Humans; Protein Biosynthesis; Ribosomes; Ricin
PubMed: 31035546
DOI: 10.3390/toxins11050241 -
PloS One 2020In the past two decades, research into the biochemical, biophysical and structural properties of the ribosome have revealed many different steps of protein translation....
In the past two decades, research into the biochemical, biophysical and structural properties of the ribosome have revealed many different steps of protein translation. Nevertheless, a complete understanding of how they lead to a rapid and accurate protein synthesis still remains a challenge. Here we consider a coarse network analysis in the bacterial ribosome formed by the connectivity between ribosomal (r) proteins and RNAs at different stages in the elongation cycle. The ribosomal networks are found to be dis-assortative and small world, implying that the structure allows for an efficient exchange of information between distant locations. An analysis of centrality shows that the second and fifth domains of 23S rRNA are the most important elements in all of the networks. Ribosomal protein hubs connect to much fewer nodes but are shown to provide important connectivity within the network (high closeness centrality). A modularity analysis reveals some of the different functional communities, indicating some known and some new possible communication pathways Our mathematical results confirm important communication pathways that have been discussed in previous research, thus verifying the use of this technique for representing the ribosome, and also reveal new insights into the collective function of ribosomal elements.
Topics: Bacteria; Computational Biology; Gene Regulatory Networks; Protein Biosynthesis; RNA, Ribosomal, 23S; Ribosomal Proteins; Ribosomes; Transcription Elongation, Genetic
PubMed: 33017414
DOI: 10.1371/journal.pone.0239700