Motoring toward pre-60S-ribosome export

2016 ◽  
Vol 23 (1) ◽  
pp. 3-4 ◽  
Author(s):  
Vadim Shchepachev ◽  
David Tollervey
Keyword(s):  
Ribosome Export

scholarly journals Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyle A. Cottrell ◽  
Ryan C. Chiou ◽  
Jason D. Weber
Keyword(s):  
Protein Synthesis ◽  
Tumor Cells ◽  
Ribosomal Proteins ◽  
Human Cancer ◽  
Mrna Translation ◽  
Ribosome Profiling ◽  
Translational Efficiency ◽  
Gene Encoding ◽  
Terminal Oligopyrimidine ◽  
Ribosome Export

AbstractTumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5′-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 largely phenocopies ARF loss, with increased protein synthesis and expression of 5′-TOP encoded proteins. The 5′-TOP regulators eIF4G1 and LARP1 are upregulated in Arf- and p53-null cells.

scholarly journals ARF suppresses 5’-terminal oligopyrimidine mRNA translation

2020 ◽  
Author(s):  
Kyle A. Cottrell ◽  
Ryan C. Chiou ◽  
Jason D. Weber
Keyword(s):  
Protein Synthesis ◽  
Tumor Cells ◽  
Ribosomal Proteins ◽  
Human Cancer ◽  
Mrna Translation ◽  
Ribosome Profiling ◽  
Translational Efficiency ◽  
Gene Encoding ◽  
Terminal Oligopyrimidine ◽  
Ribosome Export

AbstractTumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How many of the mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5’-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 caused a similar increase in 5’-TOP mRNA translation. The 5’-TOP regulators mTORC1, eIF4G1 and LARP1 are dysregulated in ARF and p53 null cells.

Eukaryotic nuclear structure explains the evolutionary rate difference of ribosome export factors

Gene ◽  
2008 ◽  
Vol 421 (1-2) ◽  
pp. 7-13 ◽  
Author(s):  
Hajime Ohyanagi ◽  
Kazuho Ikeo ◽  
Takashi Gojobori
Keyword(s):  
Nuclear Structure ◽  
Evolutionary Rate ◽  
Rate Difference ◽  
Ribosome Export

scholarly journals TOR regulates the subcellular distribution of DIM2, a KH domain protein required for cotranscriptional ribosome assembly and pre-40S ribosome export

RNA ◽  
2008 ◽  
Vol 14 (10) ◽  
pp. 2061-2073 ◽  
Author(s):  
E. Vanrobays ◽  
A. Leplus ◽  
Y. N. Osheim ◽  
A. L. Beyer ◽  
L. Wacheul ◽  
...  
Keyword(s):  
Subcellular Distribution ◽  
Ribosome Assembly ◽  
Kh Domain ◽  
Domain Protein ◽  
Ribosome Export

scholarly journals A non-canonical mechanism for Crm1-export cargo complex assembly

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Ute Fischer ◽  
Nico Schäuble ◽  
Sabina Schütz ◽  
Martin Altvater ◽  
Yiming Chang ◽  
...  
Keyword(s):  
Complex Formation ◽  
Nuclear Export ◽  
Binding Protein ◽  
Complex Assembly ◽  
Stepwise Mechanism ◽  
Weak Binding ◽  
New Type ◽  
Ribosome Export ◽  
Transport Receptor

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export.

scholarly journals CRM1 and its ribosome export adaptor NMD3 localize to the nucleolus and affect rRNA synthesis

Nucleus ◽  
2013 ◽  
Vol 4 (4) ◽  
pp. 315-325 ◽  
Author(s):  
Baoyan Bai ◽  
Henna M Moore ◽  
Marikki Laiho
Keyword(s):  
Rrna Synthesis ◽  
Ribosome Export

scholarly journals Coupled GTPase and remodelling ATPase activities form a checkpoint for ribosome export

Nature ◽  
2013 ◽  
Vol 505 (7481) ◽  
pp. 112-116 ◽  
Author(s):  
Yoshitaka Matsuo ◽  
Sander Granneman ◽  
Matthias Thoms ◽  
Rizos-Georgios Manikas ◽  
David Tollervey ◽  
...  
Keyword(s):  
Ribosome Export

scholarly journals Nucleophosmin Serves as a Rate-Limiting Nuclear Export Chaperone for the Mammalian Ribosome

2008 ◽  
Vol 28 (23) ◽  
pp. 7050-7065 ◽  
Author(s):  
Leonard B. Maggi ◽  
Michael Kuchenruether ◽  
David Y. A. Dadey ◽  
Rachel M. Schwope ◽  
Silvia Grisendi ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Cell Growth ◽  
Nuclear Export ◽  
Cellular Proliferation ◽  
Ribosomal Subunit ◽  
Mouse Development ◽  
Small Ribosomal Subunit ◽  
Ribosomal Subunits ◽  
Ribosome Export ◽  
Rate Limiting

ABSTRACT Nucleophosmin (NPM) (B23) is an essential protein in mouse development and cell growth; however, it has been assigned numerous roles in very diverse cellular processes. Here, we present a unified mechanism for NPM's role in cell growth; NPM directs the nuclear export of both 40S and 60S ribosomal subunits. NPM interacts with rRNA and large and small ribosomal subunit proteins and also colocalizes with large and small ribosomal subunit proteins in the nucleolus, nucleus, and cytoplasm. The transduction of NPM shuttling-defective mutants or the loss of Npm1 inhibited the nuclear export of both the 40S and 60S ribosomal subunits, reduced the available pool of cytoplasmic polysomes, and diminished overall protein synthesis without affecting rRNA processing or ribosome assembly. While the inhibition of NPM shuttling can block cellular proliferation, the dramatic effects on ribosome export occur prior to cell cycle inhibition. Modest increases in NPM expression amplified the export of newly synthesized rRNAs, resulting in increased rates of protein synthesis and indicating that NPM is rate limiting in this pathway. These results support the idea that NPM-regulated ribosome export is a fundamental process in cell growth.

scholarly journals Components of U3 snoRNA-containing Complexes Shuttle between Nuclei and the Cytoplasm and Differentially Localize in Nucleoli: Implications for Assembly and Function

2004 ◽  
Vol 15 (1) ◽  
pp. 281-293 ◽  
Author(s):  
Daniel J. Leary ◽  
Michael P. Terns ◽  
Sui Huang
Keyword(s):  
Rrna Processing ◽  
The Core ◽  
U3 Snorna ◽  
Pol I ◽  
Associated Proteins ◽  
Single Complex ◽  
Ribosome Export ◽  
And Function ◽  
Nucleolar Rna ◽  
Nucleolar Segregation

U3 small nucleolar RNA (snoRNA) and associated proteins are required for the processing of preribosomal RNA (pre-rRNA) and assembly of preribosomes. There are two major U3 snoRNA-containing complexes. The monoparticle contains U3 snoRNA and the core Box C/D snoRNA-associated proteins and an early preribosome-associated complex contains the monoparticle and additional factors that we refer to as preribosome-associated proteins. To address how and where the U3 snoRNA-containing preribosome assembles and how these processes are temporally and spatially regulated, we have examined the dynamics and distribution of human U3 complex-associated components in cells with active or inactive transcription of rDNA. We found that U3 complex-associated proteins shuttle between the nucleus and the cytoplasm independent of the synthesis and export of preribosomal particles, suggesting that the shuttling of these proteins may either provide opportunities for their regulation, or contribute to or modulate ribosome export. In addition, monoparticle and preribosome associated components predominantly localize to different nucleolar substructures, fibrillar components, and granular components, respectively, in active nucleoli, and partition separately into the two components during nucleolar segregation induced by inhibition of pol I transcription. Although the predominant localizations of these two sets of factors differ, there are significant areas of overlap that may represent the sites where they reside as a single complex. These results are consistent with a model in which U3 monoparticles associate with the fibrillar components of nucleoli and bind pre-rRNA during transcription, triggering recruitment of preribosome-associated proteins to assemble the complex necessary for pre-rRNA processing.

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