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Trends in Biochemical Sciences Jan 2022The conceptual origins of ribosome specialization can be traced back to the earliest days of molecular biology. Yet, this field has only recently begun to gather... (Review)
Review
The conceptual origins of ribosome specialization can be traced back to the earliest days of molecular biology. Yet, this field has only recently begun to gather momentum, with numerous studies identifying distinct heterogeneous ribosome populations across multiple species and model systems. It is proposed that some of these compositionally distinct ribosomes may be functionally specialized and able to regulate the translation of specific mRNAs. Identification and functional characterization of specialized ribosomes has the potential to elucidate a novel layer of gene expression control, at the level of translation, where the ribosome itself is a key regulatory player. In this review, we discuss different sources of ribosome heterogeneity, evidence for ribosome specialization, and also the future directions of this exciting field.
Topics: Protein Biosynthesis; RNA, Messenger; RNA, Ribosomal; Ribosomal Proteins; Ribosomes
PubMed: 34312084
DOI: 10.1016/j.tibs.2021.07.001 -
Nature Structural & Molecular Biology Nov 2022
Topics: Ribosomes; Ribosomal Proteins
PubMed: 36352145
DOI: 10.1038/s41594-022-00878-5 -
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 -
Aging Apr 2019The biosynthesis of ribosomes is a complex process that requires the coordinated action of many factors and a huge energy investment from the cell. Ribosomes are... (Review)
Review
The biosynthesis of ribosomes is a complex process that requires the coordinated action of many factors and a huge energy investment from the cell. Ribosomes are essential for protein production, and thus for cellular survival, growth and proliferation. Ribosome biogenesis is initiated in the nucleolus and includes: the synthesis and processing of ribosomal RNAs, assembly of ribosomal proteins, transport to the cytoplasm and association of ribosomal subunits. The disruption of ribosome biogenesis at various steps, with either increased or decreased expression of different ribosomal components, can promote cell cycle arrest, senescence or apoptosis. Additionally, interference with ribosomal biogenesis is often associated with cancer, aging and age-related degenerative diseases. Here, we review current knowledge on impaired ribosome biogenesis, discuss the main factors involved in stress responses under such circumstances and focus on examples with clinical relevance.
Topics: Aging; Animals; Humans; Neoplasms; Organelle Biogenesis; Ribosomal Proteins; Ribosomes
PubMed: 31026227
DOI: 10.18632/aging.101922 -
Molecules (Basel, Switzerland) Nov 2016Ribosome-inactivating proteins (RIPs) including ricin, Shiga toxin, and trichosanthin, are RNA -glycosidases that depurinate a specific adenine residue (A-4324 in rat... (Review)
Review
Ribosome-inactivating proteins (RIPs) including ricin, Shiga toxin, and trichosanthin, are RNA -glycosidases that depurinate a specific adenine residue (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. RIPs are grouped into three types according to the number of subunits and the organization of the precursor sequences. RIPs are two-domain proteins, with the active site located in the cleft between the N- and C-terminal domains. It has been found that the basic surface residues of the RIPs promote rapid and specific targeting to the ribosome and a number of RIPs have been shown to interact with the C-terminal regions of the P proteins of the ribosome. At present, the structural basis for the interaction of trichosanthin and ricin-A chain toward P2 peptide is known. This review surveys the structural features of the representative RIPs and discusses how they approach and interact with the ribosome.
Topics: Catalytic Domain; Models, Molecular; Molecular Structure; Protein Binding; Protein Interaction Domains and Motifs; Ribosome Inactivating Proteins; Ribosome Subunits; Ribosomes; Structure-Activity Relationship; Substrate Specificity
PubMed: 27879643
DOI: 10.3390/molecules21111588 -
RNA Biology Oct 2021Ribosomes are essential nanomachines responsible for all protein production in cells. Ribosome biogenesis and function are energy costly processes, they are tightly... (Review)
Review
Ribosomes are essential nanomachines responsible for all protein production in cells. Ribosome biogenesis and function are energy costly processes, they are tightly regulated to match cellular needs. In cancer, major pathways that control ribosome biogenesis and function are often deregulated to ensure cell survival and to accommodate the continuous proliferation of tumour cells. Ribosomal RNAs (rRNAs) are abundantly modified with 2'-O-methylation (Nm, ribomethylation) being one of the most common modifications. In eukaryotic ribosomes, ribomethylation is performed by the methyltransferase Fibrillarin guided by box C/D small nucleolar RNAs (snoRNAs). Accumulating evidences indicate that snoRNA expression and ribosome methylation profiles are altered in cancer. Here we review our current knowledge on differential snoRNA expression and rRNA 2'-O methylation in the context of human malignancies, and discuss the consequences and opportunities for cancer diagnostics, prognostics, and therapeutics.
Topics: Animals; Humans; Methylation; Neoplasms; RNA Processing, Post-Transcriptional; RNA, Ribosomal; RNA, Small Nucleolar; Ribosomes
PubMed: 34775914
DOI: 10.1080/15476286.2021.1991167 -
Bioscience, Biotechnology, and... Jun 2021The ribosome requires metal ions for structural stability and translational activity. These metal ions are important for stabilizing the secondary structure of ribosomal... (Review)
Review
The ribosome requires metal ions for structural stability and translational activity. These metal ions are important for stabilizing the secondary structure of ribosomal RNA, binding of ribosomal proteins to the ribosome, and for interaction of ribosomal subunits. In this review, various relationships between ribosomes and metal ions, especially Mg2+ and Zn2+, are presented. Mg2+ regulates gene expression by modulating the translational stability and synthesis of ribosomes, which in turn contribute to the cellular homeostasis of Mg2+. In addition, Mg2+ can partly complement the function of ribosomal proteins. Conversely, a reduction in the cellular concentration of Zn2+ induces replacement of ribosomal proteins, which mobilizes free-Zn2+ in the cell and represses translation activity. Evolutional relationships between these metal ions and the ribosome are also discussed.
Topics: Homeostasis; Magnesium; Ribosomes; Zinc
PubMed: 33877305
DOI: 10.1093/bbb/zbab070 -
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 -
Science Advances Jun 2023Stem cells in many systems, including germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that the...
Stem cells in many systems, including germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that the H/ACA small nuclear ribonucleoprotein (snRNP) complex that promotes pseudouridylation of ribosomal RNA (rRNA) and ribosome biogenesis is required for oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of messenger RNAs that are enriched for CAG trinucleotide repeats and encode polyglutamine-containing proteins, including differentiation factors such as RNA-binding Fox protein 1. Moreover, ribosomes were enriched at CAG repeats within transcripts during oogenesis. Increasing target of rapamycin (TOR) activity to elevate ribosome levels in H/ACA snRNP complex-depleted germlines suppressed the GSC differentiation defects, whereas germlines treated with the TOR inhibitor rapamycin had reduced levels of polyglutamine-containing proteins. Thus, ribosome biogenesis and ribosome levels can control stem cell differentiation via selective translation of CAG repeat-containing transcripts.
Topics: Ribonucleoproteins, Small Nuclear; Ribosomes; RNA, Ribosomal; Proteins; Sirolimus
PubMed: 37343092
DOI: 10.1126/sciadv.ade5492 -
Physical Review. E Oct 2023Translation is one of the most fundamental processes in the biological cell. Because of the central role that translation plays across all domains of life, the enzyme...
Translation is one of the most fundamental processes in the biological cell. Because of the central role that translation plays across all domains of life, the enzyme that carries out this process, the ribosome, is required to process information with high accuracy. This accuracy often approaches values near unity experimentally. In this paper, we model the ribosome as an information channel and demonstrate mathematically that this biological machine has information-processing capabilities that have not been recognized previously. In particular, we calculate bounds on the ribosome's theoretical Shannon capacity and numerically approximate this capacity. Finally, by incorporating estimates on the ribosome's operation time, we show that the ribosome operates at speeds safely below its capacity, allowing the ribosome to process information with an arbitrary degree of error. Our results show that the ribosome achieves a high accuracy in line with purely information-theoretic means.
Topics: Ribosomes; Protein Biosynthesis
PubMed: 37978643
DOI: 10.1103/PhysRevE.108.044404