scholarly journals SMALL ORGAN4 Is a Ribosome Biogenesis Factor Involved in 5.8S Ribosomal RNA Maturation

2020 ◽  
Vol 184 (4) ◽  
pp. 2022-2039
Author(s):  
Rosa Micol-Ponce ◽  
Raquel Sarmiento-Mañús ◽  
Sara Fontcuberta-Cervera ◽  
Adrián Cabezas-Fuster ◽  
Anne de Bures ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Ribosome Biogenesis ◽  
Rna Maturation

scholarly journals Structure of the human MTERF4–NSUN4 protein complex that regulates mitochondrial ribosome biogenesis

2012 ◽  
Vol 109 (38) ◽  
pp. 15253-15258 ◽  
Author(s):  
Henrik Spåhr ◽  
Bianca Habermann ◽  
Claes M. Gustafsson ◽  
Nils-Göran Larsson ◽  
B. Martin Hallberg
Keyword(s):  
Ribosomal Rna ◽  
Protein Complex ◽  
Ribosome Biogenesis ◽  
Rna Binding ◽  
Ribosomal Subunit ◽  
Rna Recognition ◽  
Nucleic Acid Binding ◽  
C Terminus ◽  
Mitochondrial Ribosome ◽  
Rna Maturation

Proteins crucial for the respiratory chain are translated by the mitochondrial ribosome. Mitochondrial ribosome biogenesis is therefore critical for oxidative phosphorylation capacity and disturbances are known to cause human disease. This complex process is evolutionary conserved and involves several RNA processing and modification steps required for correct ribosomal RNA maturation. We recently showed that a member of the mitochondrial transcription termination factor (MTERF) family of proteins, MTERF4, recruits NSUN4, a 5-methylcytosine RNA methyltransferase, to the large ribosomal subunit in a process crucial for mitochondrial ribosome biogenesis. Here, we describe the 3D crystal structure of the human MTERF4–NSUN4 complex determined to 2.9 Å resolution. MTERF4 is composed of structurally repeated MTERF–motifs that form a nucleic acid binding domain. NSUN4 lacks an N- or C-terminal extension that is commonly used for RNA recognition by related RNA methyltransferases. Instead, NSUN4 binds to the C-terminus of MTERF4. A positively charged surface forms an RNA binding path from the concave to the convex side of MTERF4 and further along NSUN4 all of the way into the active site. This finding suggests that both subunits of the protein complex likely contribute to RNA recognition. The interface between MTERF4 and NSUN4 contains evolutionarily conserved polar and hydrophobic amino acids, and mutations that change these residues completely disrupt complex formation. This study provides a molecular explanation for MTERF4-dependent recruitment of NSUN4 to ribosomal RNA and suggests a unique mechanism by which other members of the large MTERF-family of proteins can regulate ribosomal biogenesis.

Eukaryotic Ribosome Assembly

2019 ◽  
Vol 88 (1) ◽  
pp. 281-306 ◽  
Author(s):  
Jochen Baßler ◽  
Ed Hurt
Keyword(s):  
Ribosomal Rna ◽  
Nuclear Export ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Cryo Electron Microscopy ◽  
A Cell ◽  
Cellular Pathways ◽  
Nucleolar Rnas ◽  
Shed Light

Ribosomes, which synthesize the proteins of a cell, comprise ribosomal RNA and ribosomal proteins, which coassemble hierarchically during a process termed ribosome biogenesis. Historically, biochemical and molecular biology approaches have revealed how preribosomal particles form and mature in consecutive steps, starting in the nucleolus and terminating after nuclear export into the cytoplasm. However, only recently, due to the revolution in cryo–electron microscopy, could pseudoatomic structures of different preribosomal particles be obtained. Together with in vitro maturation assays, these findings shed light on how nascent ribosomes progress stepwise along a dynamic biogenesis pathway. Preribosomes assemble gradually, chaperoned by a myriad of assembly factors and small nucleolar RNAs, before they reach maturity and enter translation. This information will lead to a better understanding of how ribosome synthesis is linked to other cellular pathways in humans and how it can cause diseases, including cancer, if disturbed.

scholarly journals Ribosomal RNA: Maturation in a Missing Link

Nature ◽  
1970 ◽  
Vol 227 (5257) ◽  
pp. 441-441
Author(s):  
Keyword(s):  
Ribosomal Rna ◽  
Missing Link ◽  
Rna Maturation

Control of ribosomal RNA maturation in differentiating yolk sac erythroid cells

1972 ◽  
Vol 1 (4) ◽  
pp. 219-228 ◽  
Author(s):  
Antonio Fantoni ◽  
Sandra Bordin ◽  
Mario Lunadei
Keyword(s):  
Ribosomal Rna ◽  
Yolk Sac ◽  
Erythroid Cells ◽  
Rna Maturation

scholarly journals Controlling the material properties and rRNA processing function of the nucleolus using light

2019 ◽  
Vol 116 (35) ◽  
pp. 17330-17335 ◽  
Author(s):  
Lian Zhu ◽  
Tiffany M. Richardson ◽  
Ludivine Wacheul ◽  
Ming-Tzo Wei ◽  
Marina Feric ◽  
...  
Keyword(s):  
Phase Behavior ◽  
Ribosomal Rna ◽  
Material Properties ◽  
Viscoelastic Properties ◽  
Ribosome Biogenesis ◽  
Threshold Concentration ◽  
Rrna Processing ◽  
Small Proteins ◽  
Nucleolar Material ◽  
Processing Steps

The nucleolus is a prominent nuclear condensate that plays a central role in ribosome biogenesis by facilitating the transcription and processing of nascent ribosomal RNA (rRNA). A number of studies have highlighted the active viscoelastic nature of the nucleolus, whose material properties and phase behavior are a consequence of underlying molecular interactions. However, the ways in which the material properties of the nucleolus impact its function in rRNA biogenesis are not understood. Here we utilize the Cry2olig optogenetic system to modulate the viscoelastic properties of the nucleolus. We show that above a threshold concentration of Cry2olig protein, the nucleolus can be gelled into a tightly linked, low mobility meshwork. Gelled nucleoli no longer coalesce and relax into spheres but nonetheless permit continued internal molecular mobility of small proteins. These changes in nucleolar material properties manifest in specific alterations in rRNA processing steps, including a buildup of larger rRNA precursors and a depletion of smaller rRNA precursors. We propose that the flux of processed rRNA may be actively tuned by the cell through modulating nucleolar material properties, which suggests the potential of materials-based approaches for therapeutic intervention in ribosomopathies.

scholarly journals Bystin in human cancer cells: intracellular localization and function in ribosome biogenesis

2007 ◽  
Vol 404 (3) ◽  
pp. 373-381 ◽  
Author(s):  
Masaya Miyoshi ◽  
Tetsuya Okajima ◽  
Tsukasa Matsuda ◽  
Michiko N. Fukuda ◽  
Daita Nadano
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Ribosomal Rna ◽  
Mammalian Cells ◽  
Ribosome Biogenesis ◽  
Human Cancer ◽  
Intracellular Localization ◽  
Promote Cell Proliferation ◽  
Human Cancer Cell Lines ◽  
Nucleolar Stress

Although bystin has been identified as a protein potentially involved in embryo implantation (a process unique to mammals) in humans, the bystin gene is evolutionarily conserved from yeast to humans. DNA microarray data indicates that bystin is overexpressed in human cancers, suggesting that it promotes cell growth. We undertook RT (reverse transcription)–PCR and immunoblotting, and confirmed that bystin mRNA and protein respectively are expressed in human cancer cell lines, including HeLa. Subcellular fractionation identified bystin protein as nuclear and cytoplasmic, and immunofluorescence showed that nuclear bystin localizes mainly in the nucleolus. Sucrose gradient ultracentrifugation of total cytoplasmic ribosomes revealed preferential association of bystin with the 40S subunit fractions. To analyse its function, bystin expression in cells was suppressed by RNAi (RNA interference). Pulse–chase analysis of ribosomal RNA processing suggested that bystin knockdown delays processing of 18S ribosomal RNA, a component of the 40S subunit. Furthermore, this knockdown significantly inhibited cell proliferation. Our findings suggest that bystin may promote cell proliferation by facilitating ribosome biogenesis, specifically in the production of the 40S subunit. Localization of bystin to the nucleolus, the site of ribosome biogenesis, was blocked by low concentrations of actinomycin D, a reagent that causes nucleolar stress. When bystin was transiently overexpressed in HeLa cells subjected to nucleolar stress, nuclear bystin was included in particles different from the nuclear stress granules induced by heat shock. In contrast, cytoplasmic bystin was barely affected by nucleolar stress. These results suggest that, while bystin may play multiple roles in mammalian cells, a conserved function is to facilitate ribosome biogenesis required for cell growth.

scholarly journals Intranucleolar sites of ribosome biogenesis defined by the localization of early binding ribosomal proteins

2007 ◽  
Vol 177 (4) ◽  
pp. 573-578 ◽  
Author(s):  
Tim Krüger ◽  
Hanswalter Zentgraf ◽  
Ulrich Scheer
Keyword(s):  
Ribosomal Rna ◽  
Ribosomal Proteins ◽  
Live Cell Imaging ◽  
Ribosome Biogenesis ◽  
Cell Imaging ◽  
Rrna Processing ◽  
Dense Fibrillar Component ◽  
Assembly Pathway ◽  
Fibrillar Component ◽  
Processing Steps

Considerable efforts are being undertaken to elucidate the processes of ribosome biogenesis. Although various preribosomal RNP complexes have been isolated and molecularly characterized, the order of ribosomal protein (r-protein) addition to the emerging ribosome subunits is largely unknown. Furthermore, the correlation between the ribosome assembly pathway and the structural organization of the dedicated ribosome factory, the nucleolus, is not well established. We have analyzed the nucleolar localization of several early binding r-proteins in human cells, applying various methods, including live-cell imaging and electron microscopy. We have located all examined r-proteins (S4, S6, S7, S9, S14, and L4) in the granular component (GC), which is the nucleolar region where later pre-ribosomal RNA (rRNA) processing steps take place. These results imply that early binding r-proteins do not assemble with nascent pre-rRNA transcripts in the dense fibrillar component (DFC), as is generally believed, and provide a link between r-protein assembly and the emergence of distinct granules at the DFC–GC interface.

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