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International Journal of Biological... 2022Protein homeostasis is well accepted as the prerequisite for proper operation of various life activities. As the main apparatus of protein translation, ribosomes play an... (Review)
Review
Protein homeostasis is well accepted as the prerequisite for proper operation of various life activities. As the main apparatus of protein translation, ribosomes play an indispensable role in the maintenance of protein homeostasis. Nevertheless, upon stimulation of various internal and external factors, malfunction of ribosomes may be evident with the excessive production of aberrant proteins, accumulation of which can result in deleterious effects on cellular fate and even cell death. Ribosomopathies are characterized as a series of diseases caused by abnormalities of ribosomal compositions and functions. Correspondingly, cell evolves several ribosome quality control mechanisms in maintaining the quantity and quality of intracellular ribosomes, namely ribosome quality control system (RQCS). Of note, RQCS can tightly monitor the entire process from ribosome biogenesis to its degradation, with the capacity of coping with ribosomal dysfunction, including misassembled ribosomes and incorrectly synthesized ribosomal proteins. In the current literature review, we mainly introduce the RQCS and elaborate on the underlying pathogenesis of several ribosomopathies. With the in-depth understanding of ribosomal dysfunction and molecular basis of RQCS, therapeutic strategy by specifically targeting RQCS remains a promising option in treating patients with ribosomopathies and other ribosome-associated human diseases.
Topics: Eukaryota; Humans; Protein Biosynthesis; Ribosomal Proteins; Ribosomes
PubMed: 35414791
DOI: 10.7150/ijbs.70955 -
Trends in Biochemical Sciences May 2009The ribosome is an essential ribonucleoprotein enzyme, and its biogenesis is a fundamental process in all living cells. Recent X-ray crystal structures of the bacterial... (Review)
Review
The ribosome is an essential ribonucleoprotein enzyme, and its biogenesis is a fundamental process in all living cells. Recent X-ray crystal structures of the bacterial ribosome and new technologies have allowed a greater interrogation of in vitro ribosome assembly; however, substantially less is known about ribosome biogenesis in vivo. Ongoing investigations are focused on elucidating the cellular processes that facilitate biogenesis of the ribosomal subunits, and many extraribosomal factors, including modification enzymes, remodeling enzymes and GTPases, are being uncovered. Moreover, specific roles for ribosome biogenesis factors in subunit maturation are now being elaborated. Ultimately, such studies will reveal a more complete understanding of processes at work in in vivo ribosome biogenesis.
Topics: Animals; GTP Phosphohydrolases; Humans; Models, Biological; RNA, Ribosomal; Ribosomes
PubMed: 19376708
DOI: 10.1016/j.tibs.2009.01.011 -
Biochemistry. Biokhimiia Nov 2020In response to stress, eubacteria reduce the level of protein synthesis and either disassemble ribosomes into the 30S and 50S subunits or turn them into translationally... (Review)
Review
In response to stress, eubacteria reduce the level of protein synthesis and either disassemble ribosomes into the 30S and 50S subunits or turn them into translationally inactive 70S and 100S complexes. This helps the cell to solve two principal tasks: (i) to reduce the cost of protein biosynthesis under unfavorable conditions, and (ii) to preserve functional ribosomes for rapid recovery of protein synthesis until favorable conditions are restored. All known genes for ribosome silencing factors and hibernation proteins are located in the operons associated with the response to starvation as one of the stress factors, which helps the cells to coordinate the slowdown of protein synthesis with the overall stress response. It is possible that hibernation systems work as regulators that coordinate the intensity of protein synthesis with the energy state of bacterial cell. Taking into account the limited amount of nutrients in natural conditions and constant pressure of other stress factors, bacterial ribosome should remain most of time in a complex with the silencing/hibernation proteins. Therefore, hibernation is an additional stage between the ribosome recycling and translation initiation, at which the ribosome is maintained in a "preserved" state in the form of separate subunits, non-translating 70S particles, or 100S dimers. The evolution of the ribosome hibernation has occurred within a very long period of time; ribosome hibernation is a conserved mechanism that is essential for maintaining the energy- and resource-consuming process of protein biosynthesis in organisms living in changing environment under stress conditions.
Topics: Bacteria; Protein Biosynthesis; Ribosomal Proteins; Ribosomes
PubMed: 33280583
DOI: 10.1134/S0006297920110115 -
Seminars in Cell & Developmental Biology Feb 2023The ability of ribosomes to translate mRNAs into proteins is the basis of all life. While ribosomes are essential for cell viability, reduction in levels of ribosomes... (Review)
Review
The ability of ribosomes to translate mRNAs into proteins is the basis of all life. While ribosomes are essential for cell viability, reduction in levels of ribosomes can affect cell fate and developmental transitions in a tissue specific manner and can cause a plethora of related diseases called ribosomopathies. How dysregulated ribosomes homeostasis influences cell fate and developmental transitions is not fully understood. Model systems such as Drosophila and C. elegans oogenesis have been used to address these questions since defects in conserved steps in ribosome biogenesis result in stem cell differentiation and developmental defects. In this review, we first explore how ribosome levels affect stem cell differentiation. Second, we describe how ribosomal modifications and incorporation of ribosomal protein paralogs contribute to development. Third, we summarize how cells with perturbed ribosome biogenesis are sensed and eliminated during organismal growth.
Topics: Animals; Caenorhabditis elegans; Ribosomes; Ribosomal Proteins; RNA, Messenger
PubMed: 35725716
DOI: 10.1016/j.semcdb.2022.06.004 -
Methods in Molecular Biology (Clifton,... 2022Ribosomes are universally conserved ribonucleoprotein complexes involved in the decoding of the genetic information contained in messenger RNAs into proteins.... (Review)
Review
Ribosomes are universally conserved ribonucleoprotein complexes involved in the decoding of the genetic information contained in messenger RNAs into proteins. Accordingly, ribosome biogenesis is a fundamental cellular process required for functional ribosome homeostasis and to preserve satisfactory gene expression capability.Although the ribosome is universally conserved, its biogenesis shows an intriguing degree of variability across the tree of life . These differences also raise yet unresolved questions. Among them are (a) what are, if existing, the remaining ancestral common principles of ribosome biogenesis ; (b) what are the molecular impacts of the evolution history and how did they contribute to (re)shape the ribosome biogenesis pathway across the tree of life ; (c) what is the extent of functional divergence and/or convergence (functional mimicry), and in the latter case (if existing) what is the molecular basis; (d) considering the universal ribosome conservation, what is the capability of functional plasticity and cellular adaptation of the ribosome biogenesis pathway?In this review, we provide a brief overview of ribosome biogenesis across the tree of life and try to illustrate some potential and/or emerging answers to these unresolved questions.
Topics: RNA, Messenger; RNA, Ribosomal; Ribosomes
PubMed: 35796979
DOI: 10.1007/978-1-0716-2501-9_1 -
Nature Jan 1988Fashions come and go in biochemistry. The discovery that some RNAs are enzymes is reviving interest in the long-neglected ribosome. (Review)
Review
Fashions come and go in biochemistry. The discovery that some RNAs are enzymes is reviving interest in the long-neglected ribosome.
Topics: Base Sequence; History, 20th Century; Models, Biological; Molecular Biology; Molecular Sequence Data; Nucleic Acid Conformation; Protein Biosynthesis; RNA, Ribosomal; RNA, Ribosomal, 16S; Ribosomal Proteins; Ribosomes
PubMed: 3275901
DOI: 10.1038/331223a0 -
Journal of Molecular Biology Feb 2016The essential aspects of the ribosome's mechanism can be extracted from coarse-grained simulations, including the ratchet motion, the movement together of critical bases... (Review)
Review
The essential aspects of the ribosome's mechanism can be extracted from coarse-grained simulations, including the ratchet motion, the movement together of critical bases at the decoding center, and movements of the peptide tunnel lining that assist in the expulsion of the synthesized peptide. Because of its large size, coarse graining helps to simplify and to aid in the understanding of its mechanism. Results presented here utilize coarse-grained elastic network modeling to extract the dynamics, and both RNAs and proteins are coarse grained. We review our previous results, showing the well-known ratchet motions and the motions in the peptide tunnel and in the mRNA tunnel. The motions of the lining of the peptide tunnel appear to assist in the expulsion of the growing peptide chain, and clamps at the ends of the mRNA tunnel with three proteins ensure that the mRNA is held tightly during decoding and essential for the helicase activity at the entrance. The entry clamp may also assist in base recognition to ensure proper selection of the incoming tRNA. The overall precision of the ribosome machine-like motions is remarkable.
Topics: Models, Molecular; Peptides; Protein Conformation; RNA, Messenger; RNA, Transfer; Ribosomal Proteins; Ribosomes; Thermus thermophilus
PubMed: 26687034
DOI: 10.1016/j.jmb.2015.12.003 -
Physical Review. E Jan 2022The impact of ribosome exit tunnel electrostatics on the protein elongation rate or on forces acting upon the nascent polypeptide chain are currently not fully...
The impact of ribosome exit tunnel electrostatics on the protein elongation rate or on forces acting upon the nascent polypeptide chain are currently not fully elucidated. In the past, researchers have measured the electrostatic potential inside the ribosome polypeptide exit tunnel at a limited number of spatial points, at least in rabbit reticulocytes. Here we present a basic electrostatic model of the exit tunnel of the ribosome, providing a quantitative physical description of the tunnel interaction with the nascent proteins at all centro-axial points inside the tunnel. We show that a strong electrostatic screening is due to water molecules (not mobile ions) attracted to the ribosomal nucleic acid phosphate moieties buried in the immediate vicinity of the tunnel wall. We also show how the tunnel wall components and local ribosomal protein protrusions impact on the electrostatic potential profile and impede charged amino acid residues from progressing through the tunnel, affecting the elongation rate in a range of -40% to +85% when compared to the average elongation rate. The time spent by the ribosome to decode the genetic encrypted message is constrained accordingly. We quantitatively derive, at single-residue resolution, the axial forces acting on the nascent peptide from its particular sequence embedded in the tunnel. The model sheds light on how the experimental data point measurements of the potential are linked to the local structural chemistry of the inner wall, shape, and size of the tunnel. The model consistently connects experimental observations coming from different fields in molecular biology, x-ray crystallography, physical chemistry, biomechanics, and synthetic and multiomics biology. Our model should be a valuable tool to gain insight into protein synthesis dynamics, translational control, and the role of the ribosome's mechanochemistry in the cotranslational protein folding.
Topics: Animals; Peptides; Protein Biosynthesis; Protein Folding; Rabbits; Ribosomes; Static Electricity
PubMed: 35193250
DOI: 10.1103/PhysRevE.105.014409 -
Nature Communications Oct 2022The ribosome is a macromolecular machine that catalyzes the sequence-defined polymerization of L-α-amino acids into polypeptides. The catalysis of peptide bond...
The ribosome is a macromolecular machine that catalyzes the sequence-defined polymerization of L-α-amino acids into polypeptides. The catalysis of peptide bond formation between amino acid substrates is based on entropy trapping, wherein the adjacency of transfer RNA (tRNA)-coupled acyl bonds in the P-site and the α-amino groups in the A-site aligns the substrates for coupling. The plasticity of this catalytic mechanism has been observed in both remnants of the evolution of the genetic code and modern efforts to reprogram the genetic code (e.g., ribosomal incorporation of non-canonical amino acids, ribosomal ester formation). However, the limits of ribosome-mediated polymerization are underexplored. Here, rather than peptide bonds, we demonstrate ribosome-mediated polymerization of pyridazinone bonds via a cyclocondensation reaction between activated γ-keto and α-hydrazino ester monomers. In addition, we demonstrate the ribosome-catalyzed synthesis of peptide-hybrid oligomers composed of multiple sequence-defined alternating pyridazinone linkages. Our results highlight the plasticity of the ribosome's ancient bond-formation mechanism, expand the range of non-canonical polymeric backbones that can be synthesized by the ribosome, and open the door to new applications in synthetic biology.
Topics: Ribosomes; RNA, Transfer; Genetic Code; Peptides; Amino Acids; Protein Biosynthesis
PubMed: 36280685
DOI: 10.1038/s41467-022-33701-2 -
Quarterly Reviews of Biophysics Jan 2017Ribosomes are remarkable ribonucleoprotein complexes that are responsible for protein synthesis in all forms of life. They polymerize polypeptide chains programmed by... (Review)
Review
Ribosomes are remarkable ribonucleoprotein complexes that are responsible for protein synthesis in all forms of life. They polymerize polypeptide chains programmed by nucleotide sequences in messenger RNA in a mechanism mediated by transfer RNA. One of the most challenging problems in the ribosome field is to understand the mechanism of coupled translocation of mRNA and tRNA during the elongation phase of protein synthesis. In recent years, the results of structural, biophysical and biochemical studies have provided extensive evidence that translocation is based on the structural dynamics of the ribosome itself. Detailed structural analysis has shown that ribosome dynamics, like aminoacyl-tRNA selection and catalysis of peptide bond formation, is made possible by the properties of ribosomal RNA.
Topics: Animals; Biological Transport; Movement; Protein Biosynthesis; RNA, Ribosomal; Ribosomes
PubMed: 29233224
DOI: 10.1017/S0033583517000117