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Trends in Biochemical Sciences Aug 2009The molecular mechanisms by which tRNA molecules enter and transit the ribosome during mRNA translation remains elusive. However, recent genetic, biochemical and... (Review)
Review
The molecular mechanisms by which tRNA molecules enter and transit the ribosome during mRNA translation remains elusive. However, recent genetic, biochemical and structural studies offer important new findings into the ordered sequence of events underpinning the translocation process that help place the molecular mechanism within reach. In particular, new structural and kinetic insights have been obtained regarding tRNA movements through 'hybrid state' configurations. These dynamic views reveal that the macromolecular ribosome particle, like many smaller proteins, has an intrinsic capacity to reversibly sample an ensemble of similarly stable native states. Such perspectives suggest that substrates, factors and environmental cues contribute to translation regulation by helping the dynamic system navigate through a highly complex and metastable energy landscape.
Topics: Binding Sites; Models, Molecular; Nucleic Acid Conformation; Protein Biosynthesis; RNA, Messenger; RNA, Transfer; Ribosomes; Thermodynamics
PubMed: 19647434
DOI: 10.1016/j.tibs.2009.04.004 -
Acta Biochimica Et Biophysica Sinica Apr 2012This review covers data on the structural organization of functional sites in the human ribosome, namely, the messenger RNA binding center, the binding site of the... (Review)
Review
This review covers data on the structural organization of functional sites in the human ribosome, namely, the messenger RNA binding center, the binding site of the hepatitis C virus RNA internal ribosome entry site, and the peptidyl transferase center. The data summarized here have been obtained primarily by means of a site-directed cross-linking approach with application of the analogs of the respective ribosomal ligands bearing cross-linkers at the designed positions. These data are discussed taking into consideration available structural data on ribosomes from various kingdoms obtained with the use of cryo-electron microscopy, X-ray crystallography, and other approaches.
Topics: Base Sequence; Binding Sites; Cryoelectron Microscopy; Crystallography, X-Ray; Humans; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Peptidyl Transferases; RNA, Messenger; Ribosomes
PubMed: 22257731
DOI: 10.1093/abbs/gmr118 -
Blood Apr 2010Ribosomopathies compose a collection of disorders in which genetic abnormalities cause impaired ribosome biogenesis and function, resulting in specific clinical... (Review)
Review
Ribosomopathies compose a collection of disorders in which genetic abnormalities cause impaired ribosome biogenesis and function, resulting in specific clinical phenotypes. Congenital mutations in RPS19 and other genes encoding ribosomal proteins cause Diamond-Blackfan anemia, a disorder characterized by hypoplastic, macrocytic anemia. Mutations in other genes required for normal ribosome biogenesis have been implicated in other rare congenital syndromes, Schwachman-Diamond syndrome, dyskeratosis congenita, cartilage hair hypoplasia, and Treacher Collins syndrome. In addition, the 5q- syndrome, a subtype of myelodysplastic syndrome, is caused by a somatically acquired deletion of chromosome 5q, which leads to haploinsufficiency of the ribosomal protein RPS14 and an erythroid phenotype highly similar to Diamond-Blackfan anemia. Acquired abnormalities in ribosome function have been implicated more broadly in human malignancies. The p53 pathway provides a surveillance mechanism for protein translation as well as genome integrity and is activated by defects in ribosome biogenesis; this pathway appears to be a critical mediator of many of the clinical features of ribosomopathies. Elucidation of the mechanisms whereby selective abnormalities in ribosome biogenesis cause specific clinical syndromes will hopefully lead to novel therapeutic strategies for these diseases.
Topics: Genetic Diseases, Inborn; Humans; Ribosomes; Syndrome
PubMed: 20194897
DOI: 10.1182/blood-2009-10-178129 -
RNA (New York, N.Y.) Feb 2003The recent structures of the ribosome and the ribosomal subunits only heighten the intrigue of trying to understand how the ribosome is assembled. Biochemical and... (Review)
Review
The recent structures of the ribosome and the ribosomal subunits only heighten the intrigue of trying to understand how the ribosome is assembled. Biochemical and mechanistic studies have mapped out the basic series of protein binding events that occur, but we do not yet have a clear picture of the RNA conformational changes that must accompany the protein binding. Recent studies point to roles of protein folding chaperones and RNA helicases as facilitators of ribosome assembly, but the basic process of assembly seems to be encoded in the RNA sequences and can occur for the most part spontaneously in vitro, and quite possibly in vivo as well.
Topics: Bacteria; In Vitro Techniques; RNA, Ribosomal; Ribosomes
PubMed: 12554857
DOI: 10.1261/rna.2164903 -
Molecular Biology and Evolution May 2017The ribosome is imprinted with a detailed molecular chronology of the origins and early evolution of proteins. Here we show that when arranged by evolutionary phase of...
The ribosome is imprinted with a detailed molecular chronology of the origins and early evolution of proteins. Here we show that when arranged by evolutionary phase of ribosomal evolution, ribosomal protein (rProtein) segments reveal an atomic level history of protein folding. The data support a model in which aboriginal oligomers evolved into globular proteins in a hierarchical step-wise process. Complexity of assembly and folding of polypeptide increased incrementally in concert with expansion of rRNA. (i) Short random coil proto-peptides bound to rRNA, and (ii) lengthened over time and coalesced into β-β secondary elements. These secondary elements (iii) accreted and collapsed, primarily into β-domains. Domains (iv) accumulated and gained complex super-secondary structures composed of mixtures of α-helices and β-strands. Early protein evolution was guided and accelerated by interactions with rRNA. rRNA and proto-peptide provided mutual protection from chemical degradation and disassembly. rRNA stabilized polypeptide assemblies, which evolved in a stepwise process into globular domains, bypassing the immense space of random unproductive sequences. Coded proteins originated as oligomers and polymers created by the ribosome, on the ribosome and for the ribosome. Synthesis of increasingly longer products was iteratively coupled with lengthening and maturation of the ribosomal exit tunnel. Protein catalysis appears to be a late byproduct of selection for sophisticated and finely controlled assembly.
Topics: Binding Sites; Evolution, Molecular; Models, Molecular; Origin of Life; Protein Folding; Protein Structure, Secondary; RNA, Ribosomal; Ribosomal Proteins; Ribosomes; Structure-Activity Relationship
PubMed: 28201543
DOI: 10.1093/molbev/msx086 -
Biology Direct Apr 2008The origin and early evolution of the active site of the ribosome can be elucidated through an analysis of the ribosomal proteins' taxonomic block structures and their... (Comparative Study)
Comparative Study Review
BACKGROUND
The origin and early evolution of the active site of the ribosome can be elucidated through an analysis of the ribosomal proteins' taxonomic block structures and their RNA interactions. Comparison between the two subunits, exploiting the detailed three-dimensional structures of the bacterial and archaeal ribosomes, is especially informative.
RESULTS
The analysis of the differences between these two sites can be summarized as follows: 1) There is no self-folding RNA segment that defines the decoding site of the small subunit; 2) there is one self-folding RNA segment encompassing the entire peptidyl transfer center of the large subunit; 3) the protein contacts with the decoding site are made by a set of universal alignable sequence blocks of the ribosomal proteins; 4) the majority of those peptides contacting the peptidyl transfer center are made by bacterial or archaeal-specific sequence blocks.
CONCLUSION
These clear distinctions between the two subunit active sites support an earlier origin for the large subunit's peptidyl transferase center (PTC) with the decoding site of the small subunit being a later addition to the ribosome. The main implications are that a single self-folding RNA, in conjunction with a few short stabilizing peptides, formed the precursor of the modern ribosomal large subunit in association with a membrane.
Topics: Animals; Archaeal Proteins; Bacterial Proteins; Base Sequence; Evolution, Molecular; Humans; Molecular Sequence Data; Ribosomal Proteins; Ribosomes
PubMed: 18430223
DOI: 10.1186/1745-6150-3-16 -
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 -
Seminars in Hematology Apr 2011
Topics: Anemia, Diamond-Blackfan; Animals; Humans; Ribosomal Proteins; Ribosomes
PubMed: 21435502
DOI: 10.1053/j.seminhematol.2011.01.003 -
International Journal of Molecular... Jun 2019In the past few decades, studies on translation have converged towards the metaphor of a "ribosome nanomachine"; they also revealed intriguing ribosome properties... (Review)
Review
In the past few decades, studies on translation have converged towards the metaphor of a "ribosome nanomachine"; they also revealed intriguing ribosome properties challenging this view. Many studies have shown that to perform an accurate protein synthesis in a fluctuating cellular environment, ribosomes sense, transfer information and even make decisions. This complex "behaviour" that goes far beyond the skills of a simple mechanical machine has suggested that the ribosomal protein networks could play a role equivalent to nervous circuits at a molecular scale to enable information transfer and processing during translation. We analyse here the significance of this analogy and establish a preliminary link between two fields: ribosome structure-function studies and the analysis of information processing systems. This cross-disciplinary analysis opens new perspectives about the mechanisms of information transfer and processing in ribosomes and may provide new conceptual frameworks for the understanding of the behaviours of unicellular organisms.
Topics: Animals; Humans; Neural Networks, Computer; Ribosomes; Signal Transduction
PubMed: 31207893
DOI: 10.3390/ijms20122911 -
Nucleic Acids Research Sep 2020One of the main goals of ribosome profiling is to quantify the rate of protein synthesis at the level of translation. Here, we develop a method for inferring translation...
One of the main goals of ribosome profiling is to quantify the rate of protein synthesis at the level of translation. Here, we develop a method for inferring translation elongation kinetics from ribosome profiling data using recent advances in mathematical modelling of mRNA translation. Our method distinguishes between the elongation rate intrinsic to the ribosome's stepping cycle and the actual elongation rate that takes into account ribosome interference. This distinction allows us to quantify the extent of ribosomal collisions along the transcript and identify individual codons where ribosomal collisions are likely. When examining ribosome profiling in yeast, we observe that translation initiation and elongation are close to their optima and traffic is minimized at the beginning of the transcript to favour ribosome recruitment. However, we find many individual sites of congestion along the mRNAs where the probability of ribosome interference can reach $50\%$. Our work provides new measures of translation initiation and elongation efficiencies, emphasizing the importance of rating these two stages of translation separately.
Topics: Carrier Proteins; Codon, Initiator; Computational Biology; Models, Genetic; Peptide Chain Elongation, Translational; Peptide Chain Initiation, Translational; RNA, Messenger; Ribosomes; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 32821926
DOI: 10.1093/nar/gkaa678