Special Issue "rRNA Biology"

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (31 August 2018)

Special Issue Editor

Guest Editor
Dr. Jean-Jacques Diaz

Cancer Research Center of Lyon - UMR Inserm 1052 CNRS 5286 - Centre Léon Bérard, Lyon, France
Website | E-Mail
Interests: translational regulation; ribosome biology; cancer biology; cancer cell plasticity; proteomics

Special Issue Information

Dear Colleagues, 

Fourty years after the demonstration that ribosomes were the effectors of translation, new evidence suggests that we are entering an exciting novel ribosomal era in which the “passive” role of ribosomes in gene expression regulation is challenged.

Recent studies revealed unexpected roles for the eukaryotic ribosome in selective translational regulation. Numerous data show that eukaryotic ribosomes can vary in ribosomal protein (RP) composition and that ribosomes with different RP composition exhibit different translational activities. These observations led to the concept of specialized ribosomes, which was exposed in several reviews. Interestingly, ribosomal RNA composition was also shown to vary and to be associated with modulation of translational ribosomal activities. Therefore, regulation of rRNA biology per se could be an additional molecular mechanism to provide the eukaryotic ribosome with the structural and functional diversity required for its specialization. It seems timely to assemble current data potentially linking rRNA biology to ribosomal activities and ribosome specialization. We will review each step of rRNA biology emphasizing those that could directly impact ribosome structure and function, including rRNA evolution in terms of sequence, chemical modification and structure, transcriptomic and epigenetic regulation of rDNA expression, rRNA processing and assembly with RP and export, and rRNA chemical modifications. In addition, we will highlight several breakthrough technological developments that enabled us to revisit rRNA biology.

Hopefully, this Special Issue will shed some light on our “modern view of ribosomes” and respond to the palpable infatuation for ribosomes that is now affecting biologists outside of the field of ribosome biology.

Dr. Jean-Jacques Diaz
Guest Editors

Manuscript Submission Information

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Keywords

  • rRNA biology
  • rRNA function
  • rRNA epigenetics
  • rRNA processing
  • rRNA chemical modification
  • specialized ribosomes
  • 2’-O-methylation and pseudourydilation
  • rRNA base methylation
  • Ribosome biogenesis
  • translational regulation

Published Papers (6 papers)

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Research

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Open AccessArticle Knock-Down of a Novel snoRNA in Tetrahymena Reveals a Dual Role in 5.8S rRNA Processing and Generation of a 26S rRNA Fragment
Biomolecules 2018, 8(4), 128; https://doi.org/10.3390/biom8040128
Received: 13 September 2018 / Revised: 24 October 2018 / Accepted: 25 October 2018 / Published: 30 October 2018
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Abstract
In eukaryotes, 18S, 5.8S, and 28S rRNAs are transcribed as precursor molecules that undergo extensive modification and nucleolytic processing to form the mature rRNA species. Central in the process are the small nucleolar RNAs (snoRNAs). The majority of snoRNAs guide site specific chemical
[...] Read more.
In eukaryotes, 18S, 5.8S, and 28S rRNAs are transcribed as precursor molecules that undergo extensive modification and nucleolytic processing to form the mature rRNA species. Central in the process are the small nucleolar RNAs (snoRNAs). The majority of snoRNAs guide site specific chemical modifications but a few are involved in defining pre-rRNA cleavages. Here, we describe an unusual snoRNA (TtnuCD32) belonging to the box C/D subgroup from the ciliate Tetrahymena thermophila. We show that TtnuCD32 is unlikely to function as a modification guide snoRNA and that it is critical for cell viability. Cell lines with genetic knock-down of TtnuCD32 were impaired in growth and displayed two novel and apparently unrelated phenotypes. The most prominent phenotype is the accumulation of processing intermediates of 5.8S rRNA. The second phenotype is the decrease in abundance of a ~100 nt 26S rRNA fragment of unknown function. Sequence analysis demonstrated that TtnuCD32 share features with the essential snoRNA U14 but an alternative candidate (TtnuCD25) was more closely related to other U14 sequences. This, together with the fact that the observed rRNA processing phenotypes were not similar to what has been observed in U14 depleted cells, suggests that TtnuCD32 is a U14 homolog that has gained novel functions. Full article
(This article belongs to the Special Issue rRNA Biology)
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Review

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Open AccessReview Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure
Biomolecules 2018, 8(4), 125; https://doi.org/10.3390/biom8040125
Received: 20 August 2018 / Revised: 10 October 2018 / Accepted: 18 October 2018 / Published: 25 October 2018
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Abstract
Chemical modifications of RNA have recently gained new attention in biological sciences. They occur notably on messenger RNA (mRNA) and ribosomal RNA (rRNA) and are important for various cellular functions, but their molecular mechanism of action is yet to be understood in detail.
[...] Read more.
Chemical modifications of RNA have recently gained new attention in biological sciences. They occur notably on messenger RNA (mRNA) and ribosomal RNA (rRNA) and are important for various cellular functions, but their molecular mechanism of action is yet to be understood in detail. Ribosomes are large ribonucleoprotein assemblies, which synthesize proteins in all organisms. Human ribosomes, for example, carry more than 200 modified nucleotides, which are introduced during biogenesis. Chemically modified nucleotides may appear to be only scarcely different from canonical nucleotides, but modifications such as methylations can in fact modulate their chemical and topological properties in the RNA and alter or modulate the overall translation efficiency of the ribosomes resulting in dysfunction of the translation machinery. Recent functional analysis and high-resolution ribosome structures have revealed a large repertoire of modification sites comprising different modification types. In this review, we focus on 2′-O-methylations (2′-O-Me) and discuss the structural insights gained through our recent cryo electron microscopy (cryo-EM) high-resolution structural analysis of the human ribosome, such as their locations and their influence on the secondary and tertiary structures of human rRNAs. The detailed analysis presented here reveals that ribose conformations of the rRNA backbone differ when the 2′-OH hydroxyl position is methylated, with 3′-endo conformations being the default and the 2′-endo conformations being characteristic in that the associated base is flipped-out. We compare currently known 2′-O-Me sites in human rRNAs evaluated using RiboMethSeq and cryo-EM structural analysis and discuss their involvement in several human diseases. Full article
(This article belongs to the Special Issue rRNA Biology)
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Open AccessReview Pre-Ribosomal RNA Processing in Human Cells: From Mechanisms to Congenital Diseases
Biomolecules 2018, 8(4), 123; https://doi.org/10.3390/biom8040123
Received: 27 September 2018 / Revised: 19 October 2018 / Accepted: 19 October 2018 / Published: 24 October 2018
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Abstract
Ribosomal RNAs, the most abundant cellular RNA species, have evolved as the structural scaffold and the catalytic center of protein synthesis in every living organism. In eukaryotes, they are produced from a long primary transcript through an intricate sequence of processing steps that
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Ribosomal RNAs, the most abundant cellular RNA species, have evolved as the structural scaffold and the catalytic center of protein synthesis in every living organism. In eukaryotes, they are produced from a long primary transcript through an intricate sequence of processing steps that include RNA cleavage and folding and nucleotide modification. The mechanisms underlying this process in human cells have long been investigated, but technological advances have accelerated their study in the past decade. In addition, the association of congenital diseases to defects in ribosome synthesis has highlighted the central place of ribosomal RNA maturation in cell physiology regulation and broadened the interest in these mechanisms. Here, we give an overview of the current knowledge of pre-ribosomal RNA processing in human cells in light of recent progress and discuss how dysfunction of this pathway may contribute to the physiopathology of congenital diseases. Full article
(This article belongs to the Special Issue rRNA Biology)
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Open AccessReview 2′-O-Methylation of Ribosomal RNA: Towards an Epitranscriptomic Control of Translation?
Biomolecules 2018, 8(4), 106; https://doi.org/10.3390/biom8040106
Received: 17 August 2018 / Revised: 27 September 2018 / Accepted: 27 September 2018 / Published: 3 October 2018
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Abstract
Ribosomal RNA (rRNA) undergoes post-transcriptional modification of over 200 nucleotides, predominantly 2′-O-methylation (2′-O-Me). 2′-O-Methylation protects RNA from hydrolysis and modifies RNA strand flexibility but does not contribute to Watson-Crick base pairing. The contribution of 2′-O-Me to the translational capacity of ribosomes has been
[...] Read more.
Ribosomal RNA (rRNA) undergoes post-transcriptional modification of over 200 nucleotides, predominantly 2′-O-methylation (2′-O-Me). 2′-O-Methylation protects RNA from hydrolysis and modifies RNA strand flexibility but does not contribute to Watson-Crick base pairing. The contribution of 2′-O-Me to the translational capacity of ribosomes has been established. Yet, how 2′-O-Me participates in ribosome biogenesis and ribosome functioning remains unclear. The development of 2′-O-Me quantitative mapping methods has contributed to the demonstration that these modifications are not constitutive but rather provide heterogeneity to the ribosomal population. Moreover, recent advances in ribosome structure analysis and in vitro translation assays have proven, for the first time, that 2′-O-Me contributes to regulating protein synthesis. This review highlights the recent data exploring the impact of 2′-O-Me on ribosome structure and function, and the emerging idea that the rRNA epitranscriptome is involved in translational control. Full article
(This article belongs to the Special Issue rRNA Biology)
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Open AccessReview Interaction of rRNA with mRNA and tRNA in Translating Mammalian Ribosome: Functional Implications in Health and Disease
Biomolecules 2018, 8(4), 100; https://doi.org/10.3390/biom8040100
Received: 27 July 2018 / Revised: 31 August 2018 / Accepted: 13 September 2018 / Published: 26 September 2018
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Abstract
RNA-RNA interaction slowly emerges as a critical component for the smooth functioning of gene expression processes, in particular in translation where the central actor is an RNA powered molecular machine. Overall, ribosome dynamic results from sequential interactions between three main RNA species: ribosomal,
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RNA-RNA interaction slowly emerges as a critical component for the smooth functioning of gene expression processes, in particular in translation where the central actor is an RNA powered molecular machine. Overall, ribosome dynamic results from sequential interactions between three main RNA species: ribosomal, transfer and messenger RNA (rRNA, tRNA and mRNA). In recent decades, special attention has been paid to the physical principles governing codon-anticodon pairing, whereas individual RNA positioning mostly relies on ribosomal RNA framework. Here, we provide a brief overview on the actual knowledge of RNA infrastructure throughout the process of translation in mammalian cells: where and how do these physical contacts occur? What are their potential roles and functions? Are they involved in disease development? What will be the main challenges ahead? Full article
(This article belongs to the Special Issue rRNA Biology)
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Open AccessReview Turning Uridines around: Role of rRNA Pseudouridylation in Ribosome Biogenesis and Ribosomal Function
Biomolecules 2018, 8(2), 38; https://doi.org/10.3390/biom8020038
Received: 30 April 2018 / Revised: 28 May 2018 / Accepted: 31 May 2018 / Published: 5 June 2018
Cited by 2 | PDF Full-text (601 KB) | HTML Full-text | XML Full-text
Abstract
Ribosomal RNA (rRNA) is extensively edited through base methylation and acetylation, 2′-O-ribose methylation and uridine isomerization. In human rRNA, 95 uridines are predicted to by modified to pseudouridine by ribonucleoprotein complexes sharing four core proteins and differing for a RNA sequence guiding the
[...] Read more.
Ribosomal RNA (rRNA) is extensively edited through base methylation and acetylation, 2′-O-ribose methylation and uridine isomerization. In human rRNA, 95 uridines are predicted to by modified to pseudouridine by ribonucleoprotein complexes sharing four core proteins and differing for a RNA sequence guiding the complex to specific residues to be modified. Most pseudouridylation sites are placed within functionally important ribosomal domains and can influence ribosomal functional features. Information obtained so far only partially explained the degree of regulation and the consequences of pseudouridylation on ribosomal structure and function in different physiological and pathological conditions. This short review focuses on the available evidence in this topic, highlighting open questions in the field and perspectives that the development of emerging techniques is offering. Full article
(This article belongs to the Special Issue rRNA Biology)
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