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The Journal of Cell Biology Jun 2020Translation control is critical to regulate protein expression. By directly adjusting protein levels, cells can quickly respond to dynamic transitions during stem cell... (Review)
Review
Translation control is critical to regulate protein expression. By directly adjusting protein levels, cells can quickly respond to dynamic transitions during stem cell differentiation and embryonic development. Ribosomes are multisubunit cellular assemblies that mediate translation. Previously seen as invariant machines with the same composition of components in all conditions, recent studies indicate that ribosomes are heterogeneous and that different ribosome types can preferentially translate specific subsets of mRNAs. Such heterogeneity and specialized translation functions are very important in stem cells and development, as they allow cells to quickly respond to stimuli through direct changes of protein abundance. In this review, we discuss ribosome heterogeneity that arises from multiple features of rRNAs, including rRNA variants and rRNA modifications, and ribosomal proteins, including their stoichiometry, compositions, paralogues, and posttranslational modifications. We also discuss alterations of ribosome-associated proteins (RAPs), with a particular focus on their consequent specialized translational control in stem cells and development.
Topics: Cell Differentiation; Growth and Development; Humans; Protein Biosynthesis; Protein Processing, Post-Translational; RNA, Messenger; RNA, Ribosomal; Ribosomal Proteins; Ribosomes; Stem Cells
PubMed: 32330234
DOI: 10.1083/jcb.202001108 -
Cells Dec 2019Ribosomes are essential for protein synthesis in all organisms and their biogenesis and number are tightly controlled to maintain homeostasis in changing environmental... (Review)
Review
Ribosomes are essential for protein synthesis in all organisms and their biogenesis and number are tightly controlled to maintain homeostasis in changing environmental conditions. While ribosome assembly and quality control mechanisms have been extensively studied, our understanding of ribosome degradation is limited. In yeast or animal cells, ribosomes are degraded after transfer into the vacuole or lysosome by ribophagy or nonselective autophagy, and ribosomal RNA can also be transferred directly across the lysosomal membrane by RNautophagy. In plants, ribosomal RNA is degraded by the vacuolar T2 ribonuclease RNS2 after transport by autophagy-related mechanisms, although it is unknown if a selective ribophagy pathway exists in plants. In this review, we describe mechanisms of turnover of ribosomal components in animals and yeast, and, then, discuss potential pathways for degradation of ribosomal RNA and protein within the vacuole in plants.
Topics: Animals; Autophagy; Humans; Lysosomes; RNA; Ribosomes; Vacuoles
PubMed: 31835634
DOI: 10.3390/cells8121603 -
Journal of Molecular Biology May 2016The ribosome is a large two-subunit ribonucleoprotein machine that translates the genetic code in all cells, synthesizing proteins according to the sequence of the mRNA... (Review)
Review
The ribosome is a large two-subunit ribonucleoprotein machine that translates the genetic code in all cells, synthesizing proteins according to the sequence of the mRNA template. During translation, the primary substrates, transfer RNAs, pass through binding sites formed between the two subunits. Multiple interactions between the ribosomal subunits, termed intersubunit bridges, keep the ribosome intact and at the same time govern dynamics that facilitate the various steps of translation such as transfer RNA-mRNA movement. Here, we review the molecular nature of these intersubunit bridges, how they change conformation during translation, and their functional roles in the process.
Topics: Protein Biosynthesis; RNA, Messenger; RNA, Transfer; Ribosomes
PubMed: 26880335
DOI: 10.1016/j.jmb.2016.02.009 -
Cells Nov 2019The ribosome is a complex ribonucleoprotein-based molecular machine that orchestrates protein synthesis in the cell. Both ribosomal RNA and ribosomal proteins can be... (Review)
Review
The ribosome is a complex ribonucleoprotein-based molecular machine that orchestrates protein synthesis in the cell. Both ribosomal RNA and ribosomal proteins can be chemically modified by reactive oxygen species, which may alter the ribosome's functions or cause a complete loss of functionality. The oxidative damage that ribosomes accumulate during their lifespan in a cell may lead to reduced or faulty translation and contribute to various pathologies. However, remarkably little is known about the biological consequences of oxidative damage to the ribosome. Here, we provide a concise summary of the known types of changes induced by reactive oxygen species in rRNA and ribosomal proteins and discuss the existing experimental evidence of how these modifications may affect ribosome dynamics and function. We emphasize the special role that redox-active transition metals, such as iron, play in ribosome homeostasis and stability. We also discuss the hypothesis that redox-mediated ribosome modifications may contribute to adaptive cellular responses to stress.
Topics: Animals; Homeostasis; Humans; Iron; Oxidation-Reduction; Oxidative Stress; Protein Biosynthesis; RNA, Ribosomal; Reactive Oxygen Species; Ribosomes
PubMed: 31684095
DOI: 10.3390/cells8111379 -
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 -
Current Opinion in Structural Biology Apr 2018The ribosome is a macromolecular complex which is responsible for protein synthesis in all living cells according to their transcribed genetic information. Using X-ray... (Review)
Review
The ribosome is a macromolecular complex which is responsible for protein synthesis in all living cells according to their transcribed genetic information. Using X-ray crystallography and, more recently, cryo-electron microscopy (cryo-EM), the structure of the ribosome was resolved at atomic resolution in many functional and conformational states. Molecular dynamics simulations have added information on dynamics and energetics to the available structural information, thereby have bridged the gap to the kinetics obtained from single-molecule and bulk experiments. Here, we review recent computational studies that brought notable insights into ribosomal structure and function.
Topics: Animals; Cryoelectron Microscopy; Crystallography, X-Ray; Humans; Molecular Dynamics Simulation; Protein Biosynthesis; Protein Conformation; Protein Folding; RNA, Transfer; Ribosomal Proteins; Ribosomes; Thermodynamics
PubMed: 29202442
DOI: 10.1016/j.sbi.2017.11.003 -
Journal of Molecular Biology Sep 2016As high-resolution cryogenic electron microscopy (cryo-EM) structures of ribosomes proliferate, at resolutions that allow atomic interactions to be visualized, this... (Review)
Review
As high-resolution cryogenic electron microscopy (cryo-EM) structures of ribosomes proliferate, at resolutions that allow atomic interactions to be visualized, this article attempts to give a perspective on the way research on ribosome structure and dynamics may be headed, and particularly the new opportunities we have gained through recent advances in cryo-EM. It is pointed out that single-molecule FRET and cryo-EM form natural complements in the characterization of ribosome dynamics and transitions among equilibrating states of in vitro translational systems.
Topics: Biomedical Research; Cryoelectron Microscopy; Fluorescence Resonance Energy Transfer; Ribosomes
PubMed: 27178840
DOI: 10.1016/j.jmb.2016.04.034 -
Acta Crystallographica. Section D,... Jun 2017Protein folding, a process that underpins cellular activity, begins co-translationally on the ribosome. During translation, a newly synthesized polypeptide chain enters... (Review)
Review
Protein folding, a process that underpins cellular activity, begins co-translationally on the ribosome. During translation, a newly synthesized polypeptide chain enters the ribosomal exit tunnel and actively interacts with the ribosome elements - the r-proteins and rRNA that line the tunnel - prior to emerging into the cellular milieu. While understanding of the structure and function of the ribosome has advanced significantly, little is known about the process of folding of the emerging nascent chain (NC). Advances in cryo-electron microscopy are enabling visualization of NCs within the exit tunnel, allowing early glimpses of the interplay between the NC and the ribosome. Once it has emerged from the exit tunnel into the cytosol, the NC (still attached to its parent ribosome) can acquire a range of conformations, which can be characterized by NMR spectroscopy. Using experimental restraints within molecular-dynamics simulations, the ensemble of NC structures can be described. In order to delineate the process of co-translational protein folding, a hybrid structural biology approach is foreseeable, potentially offering a complete atomic description of protein folding as it occurs on the ribosome.
Topics: Animals; Cryoelectron Microscopy; Humans; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Protein Biosynthesis; Protein Folding; Ribosomes
PubMed: 28580913
DOI: 10.1107/S2059798317007446 -
RNA Biology Jan 2022The ribosome has long been thought to be a homogeneous cellular machine that constitutively and globally synthesises proteins from mRNA. However, recent studies have... (Review)
Review
The ribosome has long been thought to be a homogeneous cellular machine that constitutively and globally synthesises proteins from mRNA. However, recent studies have revealed that ribosomes are highly heterogeneous, dynamic macromolecular complexes with specialised roles in translational regulation in many organisms across the kingdoms. In this review, we summarise the current understanding of ribosome heterogeneity and the specialised functions of heterogeneous ribosomes. We also discuss specialised translation systems that utilise orthogonal ribosomes.
Topics: Protein Biosynthesis; Ribosomal Proteins; Ribosomes; RNA, Messenger; Protein Processing, Post-Translational
PubMed: 36255182
DOI: 10.1080/15476286.2022.2135299 -
Journal of Applied Physiology... Aug 2019Skeletal muscle mass responds in a remarkable manner to alterations in loading and use. It has long been clear that skeletal muscle hypertrophy can be prevented by... (Review)
Review
Skeletal muscle mass responds in a remarkable manner to alterations in loading and use. It has long been clear that skeletal muscle hypertrophy can be prevented by inhibiting RNA synthesis. Since 80% of the cell's total RNA has been estimated to be rRNA, this finding indicates that de novo production of rRNA via transcription of the corresponding genes is important for such hypertrophy to occur. Transcription of rDNA by RNA Pol I is the rate-limiting step in ribosome biogenesis, indicating in turn that this biogenesis strongly influences the hypertrophic response. The present minireview focuses on ) a brief description of the key steps in ribosome biogenesis and the relationship of this process to skeletal muscle mass and ) the coordination of ribosome biogenesis and protein synthesis for growth or atrophy, as exemplified by the intracellular AMPK and mTOR pathways.
Topics: Animals; Humans; Hypertrophy; Muscle, Skeletal; Muscular Diseases; Protein Biosynthesis; RNA, Ribosomal; Ribosomes; Transcription, Genetic
PubMed: 31219775
DOI: 10.1152/japplphysiol.00963.2018