scholarly journals MicroRNAs and long non-coding RNAs as novel regulators of ribosome biogenesis

2020 ◽  
Vol 48 (2) ◽  
pp. 595-612 ◽  
Author(s):  
Mason A. McCool ◽  
Carson J. Bryant ◽  
Susan J. Baserga
Keyword(s):  
Protein Synthesis ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Ribosomal Subunits ◽  
Additional Layer ◽  
Disease Outcomes ◽  
A Cell ◽  
Non Coding Rnas ◽  
Higher Eukaryotes ◽  
Pathological Disease

Ribosome biogenesis is the fine-tuned, essential process that generates mature ribosomal subunits and ultimately enables all protein synthesis within a cell. Novel regulators of ribosome biogenesis continue to be discovered in higher eukaryotes. While many known regulatory factors are proteins or small nucleolar ribonucleoproteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) are emerging as a novel modulatory layer controlling ribosome production. Here, we summarize work uncovering non-coding RNAs (ncRNAs) as novel regulators of ribosome biogenesis and highlight their links to diseases of defective ribosome biogenesis. It is still unclear how many miRNAs or lncRNAs are involved in phenotypic or pathological disease outcomes caused by impaired ribosome production, as in the ribosomopathies, or by increased ribosome production, as in cancer. In time, we hypothesize that many more ncRNA regulators of ribosome biogenesis will be discovered, which will be followed by an effort to establish connections between disease pathologies and the molecular mechanisms of this additional layer of ribosome biogenesis control.

scholarly journals Translation Elongation Factor 4 (LepA) Contributes to Tetracycline Susceptibility by Stalling Elongating Ribosomes

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Bin Liu ◽  
Chunlai Chen
Keyword(s):  
Protein Synthesis ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Elongation Factor ◽  
Ribosome Profiling ◽  
Translation Elongation Factor ◽  
Translation Elongation ◽  
Content Type ◽  
Elongation Phase ◽  
Profiling Analysis

ABSTRACTEven though elongation factor 4 (EF4) is the third most conserved protein in bacteria, its physiological functions remain largely unknown and its proposed molecular mechanisms are conflicting among previous studies. In the present study, we show that the growth of anEscherichia colistrain is more susceptible to tetracycline than its EF4 knockout strain. Consistent with previous studies, our results suggested that EF4 affects ribosome biogenesis when tetracycline is present. Through ribosome profiling analysis, we discovered that EF4 causes 1-nucleotide shifting of ribosomal footprints on mRNA when cells have been exposed to tetracycline. In addition, when tetracycline is present, EF4 inhibits the elongation of protein synthesis, which leads to the accumulation of ribosomes in the early segment of mRNA. Altogether, when cells are exposed to tetracycline, EF4 alters both ribosome biogenesis and the elongation phase of protein synthesis.

scholarly journals TOP mRNPs: Molecular Mechanisms and Principles of Regulation

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 969 ◽  
Author(s):  
Eric Cockman ◽  
Paul Anderson ◽  
Pavel Ivanov
Keyword(s):  
Protein Synthesis ◽  
Translational Control ◽  
Gene Networks ◽  
Cellular Response ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Mrna Translation ◽  
Ribonucleoprotein Complexes ◽  
Global Protein Synthesis ◽  
Protein Components

The cellular response to changes in the surrounding environment and to stress requires the coregulation of gene networks aiming to conserve energy and resources. This is often achieved by downregulating protein synthesis. The 5’ Terminal OligoPyrimidine (5’ TOP) motif-containing mRNAs, which encode proteins that are essential for protein synthesis, are the primary targets of translational control under stress. The TOP motif is a cis-regulatory RNA element that begins directly after the m7G cap structure and contains the hallmark invariant 5’-cytidine followed by an uninterrupted tract of 4–15 pyrimidines. Regulation of translation via the TOP motif coordinates global protein synthesis with simultaneous co-expression of the protein components required for ribosome biogenesis. In this review, we discuss architecture of TOP mRNA-containing ribonucleoprotein complexes, the principles of their assembly, and the modes of regulation of TOP mRNA translation.

scholarly journals Synergist ablation-induced hypertrophy occurs more rapidly in the plantaris than soleus muscle in rats due to different molecular mechanisms

2020 ◽  
Vol 318 (2) ◽  
pp. R360-R368 ◽  
Author(s):  
Michael D. Roberts ◽  
Christopher B. Mobley ◽  
Christopher G. Vann ◽  
Cody T. Haun ◽  
Brad J. Schoenfeld ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Satellite Cell ◽  
Soleus Muscle ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Cell Number ◽  
Proteasome Activity ◽  
20S Proteasome ◽  
Type I ◽  
Total Rna

We examined molecular mechanisms that were altered during rapid soleus (type I fiber-dominant) and plantaris (type II fiber-dominant) hypertrophy in rats. Twelve Wistar rats (3.5 mo old; 6 female, 6 male) were subjected to surgical right-leg soleus and plantaris dual overload [synergist ablation (SA)], and sham surgeries were performed on left legs (CTL). At 14 days after surgery, the muscles were dissected. Plantaris mass was 27% greater in the SA than CTL leg ( P < 0.001), soleus mass was 13% greater in the SA than CTL leg ( P < 0.001), and plantaris mass was higher than soleus mass in the SA leg ( P = 0.001). Plantaris total RNA concentrations and estimated total RNA levels (suggestive of ribosome density) were 19% and 47% greater in the SA than CTL leg ( P < 0.05), protein synthesis levels were 64% greater in the SA than CTL leg ( P = 0.038), and satellite cell number per fiber was 60% greater in the SA than CTL leg ( P = 0.003); no differences in these metrics were observed between soleus SA and CTL legs. Plantaris, as well as soleus, 20S proteasome activity was lower in the SA than CTL leg ( P < 0.05), although the degree of downregulation was greater in the plantaris than soleus muscle (−63% vs. −20%, P = 0.001). These data suggest that early-phase plantaris hypertrophy occurs more rapidly than soleus hypertrophy, which coincided with greater increases in ribosome biogenesis, protein synthesis, and satellite cell density, as well as greater decrements in 20S proteasome activity, in the plantaris muscle.

scholarly journals RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

2020 ◽  
Author(s):  
Emilie L. Cerezo ◽  
Thibault Houles ◽  
Oriane Lié ◽  
Marie-Kerguelen Sarthou ◽  
Charlotte Audoynaud ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosome Biogenesis ◽  
Mapk Pathway ◽  
Ribosomal Subunit ◽  
Mitogen Activated Protein Kinase ◽  
Particle Assembly ◽  
Ribosomal Subunits ◽  
Mitogen Activated Protein ◽  
Assembly Factor ◽  
Cell Growth And Proliferation

AbstractRibosome biogenesis lies at the nexus of various signaling pathways coordinating protein synthesis with cell growth and proliferation. This process is regulated by well-described transcriptional mechanisms, but a growing body of evidence indicates that other levels of regulation exist. Here we show that the Ras/mitogen-activated protein kinase (MAPK) pathway stimulates post-transcriptional stages of human ribosome synthesis. We identify RIOK2, a pre-40S particle assembly factor, as a new target of the MAPK-activated kinase RSK. RIOK2 phosphorylation by RSK promotes cytoplasmic maturation of late pre-40S particles, which is required for optimal protein synthesis and cell proliferation. RIOK2 phosphorylation facilitates its release from pre-40S particles and its nuclear re-import, prior to completion of small ribosomal subunits. Our results bring a detailed mechanistic link between the Ras/MAPK pathway and the maturation of human pre-40S particles, which open a hitherto poorly explored area of ribosome biogenesis.

scholarly journals Evidence for Segregation of Sphingomyelin and Cholesterol during Formation of Copi-Coated Vesicles

2000 ◽  
Vol 151 (3) ◽  
pp. 507-518 ◽  
Author(s):  
Britta Brügger ◽  
Roger Sandhoff ◽  
Sabine Wegehingel ◽  
Karin Gorgas ◽  
Jörg Malsam ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Secretory Pathway ◽  
Molecular Mechanisms ◽  
Lipid Analysis ◽  
Coated Vesicles ◽  
Early Secretory Pathway ◽  
Golgi Membranes ◽  
A Cell ◽  
Higher Eukaryotes ◽  
Specific Lipid

In higher eukaryotes, phospholipid and cholesterol synthesis occurs mainly in the endoplasmic reticulum, whereas sphingomyelin and higher glycosphingolipids are synthesized in the Golgi apparatus. Lipids like cholesterol and sphingomyelin are gradually enriched along the secretory pathway, with their highest concentration at the plasma membrane. How a cell succeeds in maintaining organelle-specific lipid compositions, despite a steady flow of incoming and outgoing transport carriers along the secretory pathway, is not yet clear. Transport and sorting along the secretory pathway of both proteins and most lipids are thought to be mediated by vesicular transport, with coat protein I (COPI) vesicles operating in the early secretory pathway. Although the protein constituents of these transport intermediates are characterized in great detail, much less is known about their lipid content. Using nano-electrospray ionization tandem mass spectrometry for quantitative lipid analysis of COPI-coated vesicles and their parental Golgi membranes, we find only low amounts of sphingomyelin and cholesterol in COPI-coated vesicles compared with their donor Golgi membranes, providing evidence for a significant segregation from COPI vesicles of these lipids. In addition, our data indicate a sorting of individual sphingomyelin molecular species. The possible molecular mechanisms underlying this segregation, as well as implications on COPI function, are discussed.

scholarly journals RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

PLoS Genetics ◽  
2021 ◽  
Vol 17 (6) ◽  
pp. e1009583
Author(s):  
Emilie L. Cerezo ◽  
Thibault Houles ◽  
Oriane Lié ◽  
Marie-Kerguelen Sarthou ◽  
Charlotte Audoynaud ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosome Biogenesis ◽  
Mapk Pathway ◽  
Ribosomal Subunit ◽  
Mitogen Activated Protein Kinase ◽  
Particle Assembly ◽  
Ribosomal Subunits ◽  
Mitogen Activated Protein ◽  
Assembly Factor ◽  
Cell Growth And Proliferation

Ribosome biogenesis lies at the nexus of various signaling pathways coordinating protein synthesis with cell growth and proliferation. This process is regulated by well-described transcriptional mechanisms, but a growing body of evidence indicates that other levels of regulation exist. Here we show that the Ras/mitogen-activated protein kinase (MAPK) pathway stimulates post-transcriptional stages of human ribosome synthesis. We identify RIOK2, a pre-40S particle assembly factor, as a new target of the MAPK-activated kinase RSK. RIOK2 phosphorylation by RSK stimulates cytoplasmic maturation of late pre-40S particles, which is required for optimal protein synthesis and cell proliferation. RIOK2 phosphorylation facilitates its release from pre-40S particles and its nuclear re-import, prior to completion of small ribosomal subunits. Our results bring a detailed mechanistic link between the Ras/MAPK pathway and the maturation of human pre-40S particles, which open a hitherto poorly explored area of ribosome biogenesis.

scholarly journals Nucleolar Organization and Functions in Health and Disease

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 526 ◽  
Author(s):  
Ursula Stochaj ◽  
Stephanie C. Weber
Keyword(s):  
Stress Responses ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Rrna Genes ◽  
Cell Physiology ◽  
Ribosomal Subunits ◽  
Diamond Blackfan Anemia ◽  
Health And Disease ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

The nucleolus is a prominent, membraneless compartment found within the nucleus of eukaryotic cells. It forms around ribosomal RNA (rRNA) genes, where it coordinates the transcription, processing, and packaging of rRNA to produce ribosomal subunits. Recent efforts to characterize the biophysical properties of the nucleolus have transformed our understanding of the assembly and organization of this dynamic compartment. Indeed, soluble macromolecules condense from the nucleoplasm to form nucleoli through a process called liquid–liquid phase separation. Individual nucleolar components rapidly exchange with the nucleoplasm and separate within the nucleolus itself to form distinct subcompartments. In addition to its essential role in ribosome biogenesis, the nucleolus regulates many aspects of cell physiology, including genome organization, stress responses, senescence and lifespan. Consequently, the nucleolus is implicated in several human diseases, such as Hutchinson–Gilford progeria syndrome, Diamond–Blackfan anemia, and various forms of cancer. This Special Issue highlights new insights into the physical and molecular mechanisms that control the architecture and diverse functions of the nucleolus, and how they break down in disease.

scholarly journals Missing Links in Epithelial-Mesenchymal Transition: Long Non-Coding RNAs Enter the Arena

2017 ◽  
Vol 44 (4) ◽  
pp. 1665-1680 ◽  
Author(s):  
Lei Wang ◽  
Fan Yang ◽  
Lin-Tao Jia ◽  
An-Gang Yang
Keyword(s):  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Biological Activities ◽  
Carcinoma Cells ◽  
Mesenchymal Transition ◽  
Master Regulators ◽  
A Cell ◽  
Non Coding Rnas ◽  
Biological Program

Cancer metastasis occurs through a series of sequential steps, which involves dissemination of tumor cells from a primary site and colonization in distant tissues. To promote the invasion-metastasis cascade, carcinoma cells usually initiate a cell-biological program called epithelial-mesenchymal transition (EMT), which is orchestrated by a set of master regulators, including TGF-β, Snail, ZEB and Twist families. The biological activities of these molecules are tightly regulated by a variety of cell-intrinsic pathways as well as extracellular cues. Recently, accumulating evidence indicates that long non-coding RNAs (lncRNAs) represent some of the most differentially expressed transcripts between primary and metastatic cancers. LncRNAs including MALAT1, HOTAIR, H19, LncRNA-ATB, and LincRNA-ROR have been reported to be involved in the process of EMT, mainly through cross-talking with master regulators of EMT. Thus, understanding the different and precise molecular mechanisms by which functional lncRNAs switch EMT on and off is important for opening up new avenues in lncRNA-directed diagnosis, prognosis, and therapeutic intervention against cancer.

scholarly journals USP16 counteracts mono-ubiquitination of RPS27a and promotes maturation of the 40S ribosomal subunit

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Christian Montellese ◽  
Jasmin van den Heuvel ◽  
Caroline Ashiono ◽  
Kerstin Dörner ◽  
André Melnik ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Synthesis ◽  
Ribosome Biogenesis ◽  
18S Rrna ◽  
Ribosomal Subunit ◽  
Rrna Processing ◽  
Ribosomal Subunits ◽  
Novel Proteins ◽  
40S Ribosomal Subunit ◽  
Final Maturation

Establishment of translational competence represents a decisive cytoplasmic step in the biogenesis of 40S ribosomal subunits. This involves final 18S rRNA processing and release of residual biogenesis factors, including the protein kinase RIOK1. To identify novel proteins promoting the final maturation of human 40S subunits, we characterized pre-ribosomal subunits trapped on RIOK1 by mass spectrometry, and identified the deubiquitinase USP16 among the captured factors. We demonstrate that USP16 constitutes a component of late cytoplasmic pre-40S subunits that promotes the removal of ubiquitin from an internal lysine of ribosomal protein RPS27a/eS31. USP16 deletion leads to late 40S subunit maturation defects, manifesting in incomplete processing of 18S rRNA and retarded recycling of late-acting ribosome biogenesis factors, revealing an unexpected contribution of USP16 to the ultimate step of 40S synthesis. Finally, ubiquitination of RPS27a appears to depend on active translation, pointing at a potential connection between 40S maturation and protein synthesis.

Nutrient-regulated gene expression in eukaryotes

2006 ◽  
Vol 73 ◽  
pp. 85-96 ◽  
Author(s):  
Richard J. Reece ◽  
Laila Beynon ◽  
Stacey Holden ◽  
Amanda D. Hughes ◽  
Karine Rébora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Control ◽  
Direct Interaction ◽  
Signalling Pathways ◽  
A Cell ◽  
One Step ◽  
Higher Eukaryotes ◽  
Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

Sign in / Sign up

Export Citation Format

Share Document