Shaping the Nascent Ribosome: AAA-ATPases in Eukaryotic Ribosome Biogenesis

Prattes, Michael; Lo, Yi-Ching; Bergler, Helmut; Stanley, Robin E.

doi:10.3390/biom9110715

Cited by 33 publications

(31 citation statements)

References 207 publications

(499 reference statements)

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“…Ribosome assembly is an efficient but complicated process ( Warner, 1999 ; Davis and Williamson, 2017 ). During this process, transient rRNA–RP interactions chaperone rRNA folding, which is essential for pre-rRNA processing and the following rRNA–RP assembly, and many other assembly factors have been identified ( Bohnsack and Bohnsack, 2019 ; Duss et al, 2019 ; Rodgers et al, 2019 ; Prattes et al, 2019 ), indicating that assembly of ribosomes, especially heterogeneous ribosomes, is significantly more complex than previously thought.…”

Section: Introductionmentioning

confidence: 99%

Ribosome heterogeneity in stem cells and development

Wang

2020

Journal of Cell Biology

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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.

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Section: Introductionmentioning

confidence: 99%

Ribosome heterogeneity in stem cells and development

Wang

2020

Journal of Cell Biology

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“…These pre-subunits are exported to the nucleoplasm, then to the cytoplasm, through separate maturation pathways involving multiple factors. Once matured in the cytoplasm, the newly-formed 40S and 60S subunits can combine during initiation of mRNA translation, to form the final 80S ribosome [3][4][5] (Figure 1). 47 pre-RNA is then pseudouridinylated by a complex containing DKC1, which is mutated in X-linked dyskeratosis congenita (XL-DC).…”

Section: Introductionmentioning

confidence: 99%

Ribosomopathies: New Therapeutic Perspectives

Orgebin

Lamoureux

Isidor

et al. 2020

Cells

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Ribosomopathies are a group of rare diseases in which genetic mutations cause defects in either ribosome biogenesis or function, given specific phenotypes. Ribosomal proteins, and multiple other factors that are necessary for ribosome biogenesis (rRNA processing, assembly of subunits, export to cytoplasm), can be affected in ribosomopathies. Despite the need for ribosomes in all cell types, these diseases result mainly in tissue-specific impairments. Depending on the type of ribosomopathy and its pathogenicity, there are many potential therapeutic targets. The present manuscript will review our knowledge of ribosomopathies, discuss current treatments, and introduce the new therapeutic perspectives based on recent research. Diamond–Blackfan anemia, currently treated with blood transfusion prior to steroids, could be managed with a range of new compounds, acting mainly on anemia, such as L-leucine. Treacher Collins syndrome could be managed by various treatments, but it has recently been shown that proteasomal inhibition by MG132 or Bortezomib may improve cranial skeleton malformations. Developmental defects resulting from ribosomopathies could be also treated pharmacologically after birth. It might thus be possible to treat certain ribosomopathies without using multiple treatments such as surgery and transplants. Ribosomopathies remain an open field in the search for new therapeutic approaches based on our recent understanding of the role of ribosomes and progress in gene therapy for curing genetic disorders.

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“…Another set of TERT partners in the nucleus are AAA-ATPases, molecular engines driving the remodeling of proteins and macromolecular assemblies [ 82 ]. Their dysfunction disturbs the formation of functional ribosomes and lead to the defects in cell proliferation and growth [ 86 ]. Specific AAA-ATPase, valosin-containing protein-like 2 (NVL2) serves as an unfoldase for the nucleolin-RNA complex.…”

Section: Discussionmentioning

confidence: 99%

Reciprocal Inhibition of Immunogenic Performance in Mice of Two Potent DNA Immunogens Targeting HCV-Related Liver Cancer

et al. 2021

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Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. A possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, but also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor-associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Additionally, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescence signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

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Shaping the Nascent Ribosome: AAA-ATPases in Eukaryotic Ribosome Biogenesis

Cited by 33 publications

References 207 publications

Ribosome heterogeneity in stem cells and development

Ribosome heterogeneity in stem cells and development

Ribosomopathies: New Therapeutic Perspectives

Reciprocal Inhibition of Immunogenic Performance in Mice of Two Potent DNA Immunogens Targeting HCV-Related Liver Cancer

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