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The Evolving Ribosome Concept
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The Evolving Ribosome Concept

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 3681

Special Issue Editor

Prof. Dr. Lasse Lindahl

E-Mail Website
Guest Editor
Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA
Interests: ribosome formation and function; RNA processing; protein-RNA complexes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ribosomes have traditionally been considered a homologous population, i.e., ribosomes are distributed evenly throughout the cytoplasm and all have the same structure and functional capabilities. In recent years, several observations suggest that this model needs revision. Emerging evidence suggests that ribosomes can be “specialized” with different compositions and functions: Some species contain paralogous ribosomal protein genes encoding (slightly) different sequences and have different intron-exon structures; rRNA can be differentially cleaved and both rRNA and ribosomal proteins can be decorated differentially with modifying groups; and protein translation may be distributed unevenly in the cell.

This special volume aims to generate a collection of papers that sheds light on the concept of specialized ribosomes and their potential importance for cell function, growth, and environmental adaptation. I invite the submission of original research papers, reviews, and theoretical considerations that contribute to the understanding of the evolving model of ribosomes and their translational properties.

Prof. Dr. Lasse Lindahl
Guest Editor

Manuscript Submission Information

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Keywords

  • specialised ribosomes
  • ribosome heterogeneity
  • differential rRNA modification
  • ribosomal protein paralog genes
  • variation ribosome composition

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Published Papers (3 papers)

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Research

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19 pages, 3346 KiB  
Article
TGF-β2 Induces Ribosome Activity, Alters Ribosome Composition and Inhibits IRES-Mediated Translation in Chondrocytes
by Guus G. H. van den Akker, Alzbeta Chabronova, Bas A. C. Housmans, Laura van der Vloet, Don A. M. Surtel, Andy Cremers, Virginie Marchand, Yuri Motorin, Marjolein M. J. Caron, Mandy J. Peffers and Tim J. M. Welting
Int. J. Mol. Sci. 2024, 25(9), 5031; https://doi.org/10.3390/ijms25095031 - 5 May 2024
Cited by 2 | Viewed by 1346
Abstract
Alterations in cell fate are often attributed to (epigenetic) regulation of gene expression. An emerging paradigm focuses on specialized ribosomes within a cell. However, little evidence exists for the dynamic regulation of ribosome composition and function. Here, we stimulated a chondrocytic cell line [...] Read more.
Alterations in cell fate are often attributed to (epigenetic) regulation of gene expression. An emerging paradigm focuses on specialized ribosomes within a cell. However, little evidence exists for the dynamic regulation of ribosome composition and function. Here, we stimulated a chondrocytic cell line with transforming growth factor beta (TGF-β2) and mapped changes in ribosome function, composition and ribosomal RNA (rRNA) epitranscriptomics. 35S Met/Cys incorporation was used to evaluate ribosome activity. Dual luciferase reporter assays were used to assess ribosomal modus. Ribosomal RNA expression and processing were determined by RT-qPCR, while RiboMethSeq and HydraPsiSeq were used to determine rRNA modification profiles. Label-free protein quantification of total cell lysates, isolated ribosomes and secreted proteins was done by LC-MS/MS. A three-day TGF-β2 stimulation induced total protein synthesis in SW1353 chondrocytic cells and human articular chondrocytes. Specifically, TGF-β2 induced cap-mediated protein synthesis, while IRES-mediated translation was not (P53 IRES) or little affected (CrPv IGR and HCV IRES). Three rRNA post-transcriptional modifications (PTMs) were affected by TGF-β2 stimulation (18S-Gm1447 downregulated, 18S-ψ1177 and 28S-ψ4598 upregulated). Proteomic analysis of isolated ribosomes revealed increased interaction with eIF2 and tRNA ligases and decreased association of eIF4A3 and heterogeneous nuclear ribonucleoprotein (HNRNP)s. In addition, thirteen core ribosomal proteins were more present in ribosomes from TGF-β2 stimulated cells, albeit with a modest fold change. A prolonged stimulation of chondrocytic cells with TGF-β2 induced ribosome activity and changed the mode of translation. These functional changes could be coupled to alterations in accessory proteins in the ribosomal proteome. Full article
(This article belongs to the Special Issue The Evolving Ribosome Concept)
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18 pages, 1276 KiB  
Perspective
Ribosome Structural Changes Dynamically Affect Ribosome Function
by Lasse Lindahl
Int. J. Mol. Sci. 2024, 25(20), 11186; https://doi.org/10.3390/ijms252011186 - 17 Oct 2024
Viewed by 809
Abstract
Ribosomes were known to be multicomponent complexes as early as the 1960s. Nonetheless, the prevailing view for decades considered active ribosomes to be a monolithic population, in which all ribosomes are identical in composition and function. This implied that ribosomes themselves did not [...] Read more.
Ribosomes were known to be multicomponent complexes as early as the 1960s. Nonetheless, the prevailing view for decades considered active ribosomes to be a monolithic population, in which all ribosomes are identical in composition and function. This implied that ribosomes themselves did not actively contribute to the regulation of protein synthesis. In this perspective, I review evidence for a different model, based on results showing that ribosomes can harbor different types of ribosomal RNA (rRNA) and ribosomal proteins (r-proteins) and, furthermore, need not contain a complete set of r-proteins. I also summarize recent results favoring the notion that such distinct types of ribosomes have different affinities for specific messenger RNAs and may execute the translation process differently. Thus, ribosomes should be considered active contributors to the regulation of protein synthesis. Full article
(This article belongs to the Special Issue The Evolving Ribosome Concept)
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8 pages, 572 KiB  
Hypothesis
The Ribosome Hypothesis: Decoding Mood Disorder Complexity
by Vandana Sharma, Karthik Swaminathan and Rammohan Shukla
Int. J. Mol. Sci. 2024, 25(5), 2815; https://doi.org/10.3390/ijms25052815 - 29 Feb 2024
Viewed by 979
Abstract
Several types of mood disorders lie along a continuum, with nebulous boundaries between them. Understanding the mechanisms that contribute to mood disorder complexity is critical for effective treatment. However, present treatments are largely centered around neurotransmission and receptor-based hypotheses, which, given the high [...] Read more.
Several types of mood disorders lie along a continuum, with nebulous boundaries between them. Understanding the mechanisms that contribute to mood disorder complexity is critical for effective treatment. However, present treatments are largely centered around neurotransmission and receptor-based hypotheses, which, given the high instance of treatment resistance, fail to adequately explain the complexities of mood disorders. In this opinion piece, based on our recent results, we propose a ribosome hypothesis of mood disorders. We suggest that any hypothesis seeking to explain the diverse nature of mood disorders must incorporate infrastructure diversity that results in a wide range of effects. Ribosomes, with their mobility across neurites and complex composition, have the potential to become specialized during stress; thus, ribosome diversity and dysregulation are well suited to explaining mood disorder complexity. Here, we first establish a framework connecting ribosomes to the current state of knowledge associated with mood disorders. Then, we describe the potential mechanisms through which ribosomes could homeostatically regulate systems to manifest diverse mood disorder phenotypes and discuss approaches for substantiating the ribosome hypothesis. Investigating these mechanisms as therapeutic targets holds promise for transdiagnostic avenues targeting mood disorders. Full article
(This article belongs to the Special Issue The Evolving Ribosome Concept)
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