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Annual Review of Biochemistry 1997The ribosome is a large multifunctional complex composed of both RNA and proteins. Biophysical methods are yielding low-resolution structures of the overall architecture... (Review)
Review
The ribosome is a large multifunctional complex composed of both RNA and proteins. Biophysical methods are yielding low-resolution structures of the overall architecture of ribosomes, and high-resolution structures of individual proteins and segments of rRNA. Accumulating evidence suggests that the ribosomal RNAs play central roles in the critical ribosomal functions of tRNA selection and binding, translocation, and peptidyl transferase. Biochemical and genetic approaches have identified specific functional interactions involving conserved nucleotides in 16S and 23S rRNA. The results obtained by these quite different approaches have begun to converge and promise to yield an unprecedented view of the mechanism of translation in the coming years.
Topics: Animals; Humans; Protein Biosynthesis; Ribosomes; Structure-Activity Relationship
PubMed: 9242921
DOI: 10.1146/annurev.biochem.66.1.679 -
Molecular Cell Nov 2018Aberrantly slow translation elicits quality control pathways initiated by the ubiquitin ligase ZNF598. How ZNF598 discriminates physiologic from pathologic translation...
Aberrantly slow translation elicits quality control pathways initiated by the ubiquitin ligase ZNF598. How ZNF598 discriminates physiologic from pathologic translation complexes and ubiquitinates stalled ribosomes selectively is unclear. Here, we find that the minimal unit engaged by ZNF598 is the collided di-ribosome, a molecular species that arises when a trailing ribosome encounters a slower leading ribosome. The collided di-ribosome structure reveals an extensive 40S-40S interface in which the ubiquitination targets of ZNF598 reside. The paucity of 60S interactions allows for different ribosome rotation states, explaining why ZNF598 recognition is indifferent to how the leading ribosome has stalled. The use of ribosome collisions as a proxy for stalling allows the degree of tolerable slowdown to be tuned by the initiation rate on that mRNA; hence, the threshold for triggering quality control is substrate specific. These findings illustrate how higher-order ribosome architecture can be exploited by cellular factors to monitor translation status.
Topics: Carrier Proteins; HEK293 Cells; Humans; Protein Biosynthesis; RNA, Messenger; Ribosomes; Ubiquitin; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 30293783
DOI: 10.1016/j.molcel.2018.08.037 -
Current Opinion in Neurobiology Aug 2017Neurons are amongst the most structurally complex cells and exhibit a high degree of spatial compartmentalization. Also, neurons exhibit rapid and dynamic signaling by... (Review)
Review
Neurons are amongst the most structurally complex cells and exhibit a high degree of spatial compartmentalization. Also, neurons exhibit rapid and dynamic signaling by processing information in a precise and, sometimes, spatially-restricted manner. The signaling that occurs in axons and dendrites necessitates the maintenance and modification of their local proteomes. Local translation of mRNAs into protein is one solution that neurons use to meet synaptic demand and activity. Here we review some of the key findings and recent discoveries that have shaped our understanding of local translation in neuronal function and highlight important new techniques that might pave the way for new insights.
Topics: Animals; Humans; Neurons; Neurophysiology; Protein Biosynthesis; RNA Transport; RNA, Messenger; Signal Transduction
PubMed: 28633045
DOI: 10.1016/j.conb.2017.05.005 -
International Journal of Molecular... Jan 2020Expression systems for highly toxic protein genes must be conditional and suppress leakage expression to almost zero because even faint leakage expression may kill host... (Review)
Review
Expression systems for highly toxic protein genes must be conditional and suppress leakage expression to almost zero because even faint leakage expression may kill host cells, inhibit host growth, and cause loss of plasmids containing the toxic protein genes. The most widely used conditional expression systems are controlled only at the transcriptional level, and complete suppression of leakage expression is challenging. Recent progress on translational control has enabled construction of dual transcriptional-translational control systems in which leakage expression is strongly suppressed. This review summarizes the principles, features, and practical examples of dual transcriptional-translational control systems in bacteria, and provides future perspectives on these systems.
Topics: Bacterial Proteins; Escherichia coli; Gene Expression Regulation, Bacterial; Genes, Bacterial; Plasmids; Protein Biosynthesis; Protein Processing, Post-Translational; RNA, Antisense; RNA, Catalytic; Riboswitch; Transcription, Genetic
PubMed: 31973139
DOI: 10.3390/ijms21030705 -
Cell Cycle (Georgetown, Tex.) Nov 2011
Topics: Peptide Initiation Factors; Protein Biosynthesis; RNA, Messenger; RNA-Binding Proteins; Ribosomes; Eukaryotic Translation Initiation Factor 5A
PubMed: 22037286
DOI: 10.4161/cc.10.21.17850 -
Annual Review of Genomics and Human... 2014Nonsense suppression therapy encompasses approaches aimed at suppressing translation termination at in-frame premature termination codons (PTCs, also known as nonsense... (Review)
Review
Nonsense suppression therapy encompasses approaches aimed at suppressing translation termination at in-frame premature termination codons (PTCs, also known as nonsense mutations) to restore deficient protein function. In this review, we examine the current status of PTC suppression as a therapy for genetic diseases caused by nonsense mutations. We discuss what is currently known about the mechanism of PTC suppression as well as therapeutic approaches under development to suppress PTCs. The approaches considered include readthrough drugs, suppressor tRNAs, PTC pseudouridylation, and inhibition of nonsense-mediated mRNA decay. We also discuss the barriers that currently limit the clinical application of nonsense suppression therapy and suggest how some of these difficulties may be overcome. Finally, we consider how PTC suppression may play a role in the clinical treatment of genetic diseases caused by nonsense mutations.
Topics: Codon, Nonsense; Genetic Diseases, Inborn; Humans; Nonsense Mediated mRNA Decay; Peptide Chain Termination, Translational; Protein Biosynthesis
PubMed: 24773318
DOI: 10.1146/annurev-genom-091212-153527 -
Journal of Applied Physiology... Aug 2019
Topics: Animals; Humans; Muscle Proteins; Muscle, Skeletal; Muscular Diseases; Myocardium; Protein Biosynthesis; Protein Processing, Post-Translational
PubMed: 31446832
DOI: 10.1152/japplphysiol.00497.2019 -
Philosophical Transactions of the Royal... May 2013The historical origins and current interpretation of the molecular chaperone concept are presented, with the emphasis on the distinction between folding chaperones and... (Review)
Review
The historical origins and current interpretation of the molecular chaperone concept are presented, with the emphasis on the distinction between folding chaperones and assembly chaperones. Definitions of some basic terms in this field are offered and misconceptions pointed out. Two examples of assembly chaperone are discussed in more detail: the role of numerous histone chaperones in fundamental nuclear processes and the co-operation of assembly chaperones with folding chaperones in the production of the world's most important enzyme.
Topics: Gene Expression Regulation; Histones; Molecular Chaperones; Protein Biosynthesis; Protein Conformation; Protein Folding
PubMed: 23530255
DOI: 10.1098/rstb.2011.0398 -
Proceedings of the National Academy of... Aug 2005
Review
Topics: Biological Transport; Cell Nucleus; Cytoplasm; Protein Biosynthesis; RNA, Transfer; Transfer RNA Aminoacylation
PubMed: 16061803
DOI: 10.1073/pnas.0504843102 -
Proceedings of the National Academy of... Dec 2008
Review
Topics: Protein Biosynthesis; RNA Editing; RNA, Transfer, Amino Acyl
PubMed: 19057010
DOI: 10.1073/pnas.0810781106