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Molekuliarnaia Biologiia 2014Ribosome is a macromolecular complex, which is responsible for protein biosynthesis. Two bacterial ribosomal subunits contain more than 4000 RNA nucleotides and 50... (Review)
Review
Ribosome is a macromolecular complex, which is responsible for protein biosynthesis. Two bacterial ribosomal subunits contain more than 4000 RNA nucleotides and 50 proteins. Ribosome assembly is a complicated multi-step process, vitally important for cell. In this review we summarised present-day conceptions about the mechanism of the bacterial ribosome assembly in the cell and in vitro model systems. Some details of the assembly of this machinery are still-unknown.
Topics: Escherichia coli; GTP Phosphohydrolases; RNA Helicases; RNA, Ribosomal; Ribosomal Proteins; Ribosome Subunits, Large, Bacterial; Ribosome Subunits, Small, Bacterial; Ribosomes
PubMed: 25842841
DOI: No ID Found -
Science Progress 2004The role of the bacterial ribosome in the cellular response to environmental stress has been widely considered over last decade. Certain ribosome-associated proteins... (Review)
Review
The role of the bacterial ribosome in the cellular response to environmental stress has been widely considered over last decade. Certain ribosome-associated proteins have been shown to induce conformational changes that lead to the formation of inactive forms of ribosomes that are presumed to be more stable during stationary phase. This was found to aid the survival of bacteria in this phase. Such proteins include ribosome modulation factor (RMF), YfiA and YhbH. Examining the influence of RMF on the survival of E. coli under heat, acid and osmotic stress showed that it was important for bacterial viability under these environmental pressures. However, the mechanism by which this protein exerts its effect has not been fully elucidated. The present work reviews the involvement of ribosomes in determining cell behaviour during stress. It focuses on the action of the ribosome-associated proteins and their role in inactivating ribosomes for preserving their integrity and aiding cell survival under stress.
Topics: Bacterial Physiological Phenomena; Bacterial Proteins; Oxidative Stress; Ribosomal Proteins; Ribosomes
PubMed: 15884656
DOI: 10.3184/003685004783238517 -
Cells Mar 2020The human 80S ribosome is the cellular nucleoprotein nanomachine in charge of protein synthesis that is profoundly affected during cancer transformation by oncogenic... (Review)
Review
The human 80S ribosome is the cellular nucleoprotein nanomachine in charge of protein synthesis that is profoundly affected during cancer transformation by oncogenic proteins and provides cancerous proliferating cells with proteins and therefore biomass. Indeed, cancer is associated with an increase in ribosome biogenesis and mutations in several ribosomal proteins genes are found in ribosomopathies, which are congenital diseases that display an elevated risk of cancer. Ribosomes and their biogenesis therefore represent attractive anti-cancer targets and several strategies are being developed to identify efficient and specific drugs. Homoharringtonine (HHT) is the only direct ribosome inhibitor currently used in clinics for cancer treatments, although many classical chemotherapeutic drugs also appear to impact on protein synthesis. Here we review the role of the human ribosome as a medical target in cancer, and how functional and structural analysis combined with chemical synthesis of new inhibitors can synergize. The possible existence of oncoribosomes is also discussed. The emerging idea is that targeting the human ribosome could not only allow the interference with cancer cell addiction towards protein synthesis and possibly induce their death but may also be highly valuable to decrease the levels of oncogenic proteins that display a high turnover rate (MYC, MCL1). Cryo-electron microscopy (cryo-EM) is an advanced method that allows the visualization of human ribosome complexes with factors and bound inhibitors to improve our understanding of their functioning mechanisms mode. Cryo-EM structures could greatly assist the foundation phase of a novel drug-design strategy. One goal would be to identify new specific and active molecules targeting the ribosome in cancer such as derivatives of cycloheximide, a well-known ribosome inhibitor.
Topics: Cryoelectron Microscopy; Drug Design; Humans; Models, Molecular; Neoplasms; Protein Biosynthesis; Ribosomes
PubMed: 32151059
DOI: 10.3390/cells9030629 -
Cold Spring Harbor Perspectives in... Sep 2010The modern ribosome was largely formed at the time of the last common ancestor, LUCA. Hence its earliest origins likely lie in the RNA world. Central to its development... (Review)
Review
The modern ribosome was largely formed at the time of the last common ancestor, LUCA. Hence its earliest origins likely lie in the RNA world. Central to its development were RNAs that spawned the modern tRNAs and a symmetrical region deep within the large ribosomal RNA, (rRNA), where the peptidyl transferase reaction occurs. To understand pre-LUCA developments, it is argued that events that are coupled in time are especially useful if one can infer a likely order in which they occurred. Using such timing events, the relative age of various proteins and individual regions within the large rRNA are inferred. An examination of the properties of modern ribosomes strongly suggests that the initial peptides made by the primitive ribosomes were likely enriched for l-amino acids, but did not completely exclude d-amino acids. This has implications for the nature of peptides made by the first ribosomes. From the perspective of ribosome origins, the immediate question regarding coding is when did it arise rather than how did the assignments evolve. The modern ribosome is very dynamic with tRNAs moving in and out and the mRNA moving relative to the ribosome. These movements may have become possible as a result of the addition of a template to hold the tRNAs. That template would subsequently become the mRNA, thereby allowing the evolution of the code and making an RNA genome useful. Finally, a highly speculative timeline of major events in ribosome history is presented and possible future directions discussed.
Topics: Evolution, Molecular; RNA, Ribosomal; RNA, Transfer; Ribosomes
PubMed: 20534711
DOI: 10.1101/cshperspect.a003483 -
Trends in Microbiology Jul 2008Ribosome research has undergone astonishing progress in recent years. Crystal structures have shed light on the functional properties of the translation machinery and... (Review)
Review
Ribosome research has undergone astonishing progress in recent years. Crystal structures have shed light on the functional properties of the translation machinery and revealed how the striking architecture of the ribosome is ingeniously designed as the framework for its unique capabilities: precise decoding, substrate-mediated peptide-bond formation and efficient polymerase activity. New findings include the two concerted elements of tRNA translocation: sideways shift and a ribosomal-navigated rotatory motion; the dynamics of the nascent-chain exit tunnel and the shelter formed by the ribosome-bound trigger-factor, which acts as a chaperone to prevent nascent-chain aggregation and misfolding. The availability of these structures has also illuminated the action, selectivity, resistance and synergism of antibiotics that target ribosomes.
Topics: Animals; Base Sequence; Cryoelectron Microscopy; Crystallography, X-Ray; Eukaryotic Cells; Humans; Models, Molecular; Molecular Sequence Data; Prokaryotic Cells; Protein Biosynthesis; RNA, Transfer; Ribosomal Proteins; Ribosomes
PubMed: 18547810
DOI: 10.1016/j.tim.2008.05.001 -
Wiley Interdisciplinary Reviews. RNA May 2021Ribosomal protein genes are among the most highly expressed genes in most cell types. Their products are generally essential for ribosome synthesis, which is the... (Review)
Review
Ribosomal protein genes are among the most highly expressed genes in most cell types. Their products are generally essential for ribosome synthesis, which is the cornerstone for cell growth and proliferation. Many cellular resources are dedicated to producing ribosomal proteins and thus this process needs to be regulated in ways that carefully balance the supply of nascent ribosomal proteins with the demand for new ribosomes. Ribosomal protein genes have classically been viewed as a uniform interconnected regulon regulated in eukaryotic cells by target of rapamycin and protein kinase A pathway in response to changes in growth conditions and/or cellular status. However, recent literature depicts a more complex picture in which the amount of ribosomal proteins produced varies between genes in response to two overlapping regulatory circuits. The first includes the classical general ribosome-producing program and the second is a gene-specific feature responsible for fine-tuning the amount of ribosomal proteins produced from each individual ribosomal gene. Unlike the general pathway that is mainly controlled at the level of transcription and translation, this specific regulation of ribosomal protein genes is largely achieved through changes in pre-mRNA splicing efficiency and mRNA stability. By combining general and specific regulation, the cell can coordinate ribosome production, while allowing functional specialization and diversity. Here we review the many ways ribosomal protein genes are regulated, with special focus on the emerging role of posttranscriptional regulatory events in fine-tuning the expression of ribosomal protein genes and its role in controlling the potential variation in ribosome functions. This article is categorized under: Translation > Ribosome Biogenesis Translation > Ribosome Structure/Function Translation > Translation Regulation.
Topics: Eukaryotic Cells; Gene Expression Regulation; RNA Stability; Ribosomal Proteins; Ribosomes
PubMed: 33038057
DOI: 10.1002/wrna.1632 -
Annual Review of Biophysics 2010Our current understanding of the mechanism of translation is based on nearly fifty years of biochemical and biophysical studies. This mechanism, which requires the... (Review)
Review
Our current understanding of the mechanism of translation is based on nearly fifty years of biochemical and biophysical studies. This mechanism, which requires the ribosome to manipulate tRNA and step repetitively along the mRNA, implies movement. High-resolution structures of the ribosome and its ligands have recently described translation in atomic detail, capturing the endpoints of large-scale rearrangements of the ribosome. Direct observation of the dynamic events that underlie the mechanism of translation is challenged by ensemble averaging in bulk solutions. Single-molecule methods, which eliminate these averaging effects, have emerged as powerful tools to probe the mechanism of translation. Single-molecule fluorescence experiments have described the dynamic motion of the ribosome and tRNA. Single-molecule force measurements have directly probed the forces stabilizing ribosomal complexes. Recent developments have allowed real-time observation of ribosome movement and dynamics during translation. This review covers the contributions of single-molecule studies to our understanding of the dynamic nature of translation.
Topics: Eukaryotic Cells; Fluorescence; Models, Biological; Prokaryotic Cells; Protein Biosynthesis; RNA, Messenger; RNA, Transfer; Ribosomes
PubMed: 20192783
DOI: 10.1146/annurev.biophys.093008.131427 -
Biochimie Aug 2006The ribosome is a molecular machine that synthesizes polypeptides from aminoacyl-tRNAs according to the sequence of the mRNA template. Codon reading by the anticodon of... (Review)
Review
The ribosome is a molecular machine that synthesizes polypeptides from aminoacyl-tRNAs according to the sequence of the mRNA template. Codon reading by the anticodon of tRNA is controlled by a network of ribosome contacts that are specific for each position of the codon-anticodon duplex and involve A-minor RNA interactions. Rapid and accurate tRNA selection is accomplished by switching the conformation of the decoding site between accepting and rejecting mode, regardless of the thermodynamic stability of the respective codon-anticodon complexes or their interactions at the decoding site. The forward reactions are particularly sensitive to mismatches and determine the variations in the extent of misreading of near-cognate codons, both during initial selection and proofreading. This review emphasizes the progress made in understanding the mechanisms that determine recognition and selection of tRNA by the translational machinery.
Topics: Anticodon; Base Pair Mismatch; Codon; GTP Phosphohydrolases; Nucleic Acid Conformation; Protein Biosynthesis; RNA, Transfer; Ribosomes
PubMed: 16716484
DOI: 10.1016/j.biochi.2006.04.013 -
Nature Reviews. Microbiology Nov 2005Many clinically useful antibiotics exert their antimicrobial effects by blocking protein synthesis on the bacterial ribosome. The structure of the ribosome has recently... (Review)
Review
Many clinically useful antibiotics exert their antimicrobial effects by blocking protein synthesis on the bacterial ribosome. The structure of the ribosome has recently been determined by X-ray crystallography, revealing the molecular details of the antibiotic-binding sites. The crystal data explain many earlier biochemical and genetic observations, including how drugs exercise their inhibitory effects, how some drugs in combination enhance or impede each other's binding, and how alterations to ribosomal components confer resistance. The crystal structures also provide insight as to how existing drugs might be derivatized (or novel drugs created) to improve binding and circumvent resistance.
Topics: Anti-Bacterial Agents; Bacteria; Binding Sites; Drug Resistance; Macrolides; Models, Molecular; Ribosomal Proteins; Ribosomes
PubMed: 16261170
DOI: 10.1038/nrmicro1265 -
Current Opinion in Chemical Biology Dec 2008Protein synthesis is inherently a dynamic process, requiring both small-scale and large-scale movements of tRNA and mRNA. It has long been suspected that these movements... (Review)
Review
Protein synthesis is inherently a dynamic process, requiring both small-scale and large-scale movements of tRNA and mRNA. It has long been suspected that these movements might be coupled to conformational changes in the ribosome, and in its RNA moieties in particular. Recently, the nature of ribosome structural dynamics has begun to emerge from a combination of approaches, most notably cryo-EM, X-ray crystallography, and FRET. Ribosome movement occurs both on a grand scale, as in the intersubunit rotational movements that are coupled to tRNA-mRNA translocation, and in intricate localized rearrangements such as those that accompany codon-anticodon recognition and peptide bond formation. In spite of much progress, our understanding of the mechanics of translation is now beset with countless new questions, reflecting the vast molecular architecture of the ribosome itself.
Topics: Movement; Peptidyl Transferases; RNA, Ribosomal; Ribosome Subunits, Small; Ribosomes
PubMed: 18848900
DOI: 10.1016/j.cbpa.2008.08.037