scholarly journals Novel Stress-responsive Genes EMG1 and NOP14 Encode Conserved, Interacting Proteins Required for 40S Ribosome Biogenesis

2001 ◽  
Vol 12 (11) ◽  
pp. 3644-3657 ◽  
Author(s):  
Phillip C. C. Liu ◽  
Dennis J. Thiele
Keyword(s):  
Gene Expression ◽  
Ribosome Biogenesis ◽  
Expression Patterns ◽  
Ribosomal Subunit ◽  
Temperature Sensitive ◽  
Physical Interaction ◽  
Ribosomal Protein Genes ◽  
Yeast Saccharomyces Cerevisiae ◽  
40S Ribosomal Subunit ◽  
Responsive Gene

Under stressful conditions organisms adjust the synthesis, processing, and trafficking of molecules to allow survival from and recovery after stress. In baker's yeast Saccharomyces cerevisiae, the cellular production of ribosomes is tightly matched with environmental conditions and nutrient availability through coordinate transcriptional regulation of genes involved in ribosome biogenesis. On the basis of stress-responsive gene expression and functional studies, we have identified a novel, evolutionarily conserved gene, EMG1, that has similar stress-responsive gene expression patterns as ribosomal protein genes and is required for the biogenesis of the 40S ribosomal subunit. The Emg1 protein is distributed throughout the cell; however, its nuclear localization depends on physical interaction with a newly characterized nucleolar protein, Nop14. Yeast depleted of Nop14 or harboring a temperature-sensitive allele of emg1 have selectively reduced levels of the 20S pre-rRNA and mature18S rRNA and diminished cellular levels of the 40S ribosomal subunit. Neither Emg1 nor Nop14 contain any characterized functional motifs; however, isolation and functional analyses of mammalian orthologues of Emg1 and Nop14 suggest that these proteins are functionally conserved among eukaryotes. We conclude that Emg1 and Nop14 are novel proteins whose interaction is required for the maturation of the 18S rRNA and for 40S ribosome production.

Requirements for the nuclear export of the small ribosomal subunit

2002 ◽  
Vol 115 (14) ◽  
pp. 2985-2995 ◽  
Author(s):  
Terence I. Moy ◽  
Pamela A. Silver
Keyword(s):  
Nuclear Export ◽  
Ribosome Biogenesis ◽  
Large Scale ◽  
Ribosomal Subunit ◽  
Small Subunit ◽  
Temperature Sensitive ◽  
Yeast Saccharomyces Cerevisiae ◽  
Small Ribosomal Subunit ◽  
Factors Affecting ◽  
The Stability

Eukaryotic ribosome biogenesis requires multiple steps of nuclear transport because ribosomes are assembled in the nucleus while protein synthesis occurs in the cytoplasm. Using an in situ RNA localization assay in the yeast Saccharomyces cerevisiae, we determined that efficient nuclear export of the small ribosomal subunit requires Yrb2, a factor involved in Crm1-mediated export. Furthermore, in cells lacking YRB2, the stability and abundance of the small ribosomal subunit is decreased in comparison with the large ribosomal subunit. To identify additional factors affecting small subunit export, we performed a large-scale screen of temperature-sensitive mutants. We isolated new alleles of several nucleoporins and Ran-GTPase regulators. Together with further analysis of existing mutants,we show that nucleoporins previously shown to be defective in ribosomal assembly are also defective in export of the small ribosomal subunit.

CDC68, a yeast gene that affects regulation of cell proliferation and transcription, encodes a protein with a highly acidic carboxyl terminus

1991 ◽  
Vol 11 (11) ◽  
pp. 5718-5726
Author(s):  
A Rowley ◽  
R A Singer ◽  
G C Johnston
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cycle Performance ◽  
Carboxyl Terminus ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Negative Effects ◽  
Yeast Saccharomyces Cerevisiae ◽  
Acid Protein ◽  
Mutant Cells

The cell cycle of the budding yeast Saccharomyces cerevisiae has been investigated through the study of conditional cdc mutations that specifically affect cell cycle performance. Cells bearing the cdc68-1 mutation (J. A. Prendergast, L. E. Murray, A. Rowley, D. R. Carruthers, R. A. Singer, and G. C. Johnston, Genetics 124:81-90, 1990) are temperature sensitive for the performance of the G1 regulatory event, START. Here we describe the CDC68 gene and present evidence that the CDC68 gene product functions in transcription. CDC68 encodes a 1,035-amino-acid protein with a highly acidic and serine-rich carboxyl terminus. The abundance of transcripts from several unrelated genes is decreased in cdc68-1 mutant cells after transfer to the restrictive temperature, while at least one transcript, from the HSP82 gene, persists in an aberrant fashion. Thus, the cdc68-1 mutation has both positive and negative effects on gene expression. Our findings complement those of Malone et al. (E. A. Malone, C. D. Clark, A. Chiang, and F. Winston, Mol. Cell. Biol. 11:5710-5717, 1991), who have independently identified the CDC68 gene (as SPT16) as a transcriptional suppressor of delta-insertion mutations. Among transcripts that rapidly become depleted in cdc68-1 mutant cells are those of the G1 cyclin genes CLN1, CLN2, and CLN3/WHI1/DAF1, whose activity has been previously shown to be required for the performance of START. The decreased abundance of cyclin transcripts in cdc68-1 mutant cells, coupled with the suppression of cdc68-1-mediated START arrest by the CLN2-1 hyperactive allele of CLN2, shows that the CDC68 gene affects START through cyclin gene expression.

scholarly journals The High-resolution Timeline of Expression of Ribosomal Protein Genes in Yeast

2017 ◽  
Author(s):  
Xueling Li ◽  
Gang Chen ◽  
Bernard Fongang ◽  
Dirar Homouz ◽  
Maga Rowicka ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Center Of Mass ◽  
Regulatory Elements ◽  
Ribosomal Protein Genes ◽  
Translational Initiation ◽  
Expression Of Genes ◽  
Expression Time

AbstractThe yeast ribosome is a complex molecular machine built from four rRNAs and over 70 r-proteins. Ribosome biogenesis involves ordered incorporation of ribosomal proteins, accompanied by and association and dissociation of other proteins specific to different stages of the process. By model-based analysis of temporal profiles of gene expression in a metabolically regulated system, we obtained an accurate, high-resolution estimation of the time of expression of genes coding for proteins involved in ribosome biogenesis. The ribosomal proteins are expressed in a sequence that spans approximately 25-minutes under metabolically regulated conditions. The genes coding for proteins incorporated into the mature ribosome are expressed significantly later than those that are not incorporated, but are otherwise involved in ribosome biogenesis, localization and assembly, rRNA processing and translational initiation. The relative expression time of proteins localized within specified neighborhood is significantly correlated with the distance to the centroid of the mature ribosome: protein localized closer to the center of mass of the entire complex tend to be expressed earlier than the protein localized further from the center. The timeline of gene expression also agrees with the known dependencies between recruitment of specific proteins into the mature ribosome. These findings are consistent in two independent experiments. We have further identified regulatory elements correlated with the time of regulation, including a possible dependence of expression time on the position of the RAP1 binding site within the 5’UTR.

scholarly journals MYC regulates ribosome biogenesis and mitochondrial gene expression programs through interaction with Host Cell Factor-1

2020 ◽  
Author(s):  
Tessa M. Popay ◽  
Jing Wang ◽  
Clare M. Adams ◽  
Simona G. Codreanu ◽  
Stacy Sherrod ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Ribosome Biogenesis ◽  
Focal Point ◽  
Mitochondrial Gene ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Cancer Therapies ◽  
Host Cell Factor

ABSTRACTThe oncoprotein transcription factor MYC is a major driver of malignancy and a highly-validated but challenging target for development of anti-cancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here, we interrogate how one MYC co-factor, Host Cell Factor (HCF)-1, contributes to MYC activity in a Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets, and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies.

scholarly journals Chaperone-E3 Ligase Complex HSP70-CHIP Mediates Ubiquitination of Ribosomal Protein S3

2018 ◽  
Vol 19 (9) ◽  
pp. 2723 ◽  
Author(s):  
Inwoo Hwang ◽  
Sung-Woo Cho ◽  
Jee-Yin Ahn
Keyword(s):  
Ribosomal Protein ◽  
Ribosome Biogenesis ◽  
Ribosomal Subunit ◽  
E3 Ligase ◽  
Interacting Protein ◽  
Akt Activation ◽  
Protein Levels ◽  
40S Ribosomal Subunit ◽  
Subsequent Degradation ◽  
Ribosomal Protein S3

In addition to its role in ribosome biogenesis, ribosomal protein S3 (RPS3), a component of the 40S ribosomal subunit, has been suggested to possess several extraribosomal functions, including an apoptotic function. In this study, we demonstrated that in the mouse brain, the protein levels of RPS3 were altered by the degree of nutritional starvation and correlated with neuronal apoptosis. After endurable short-term starvation, the apoptotic function of RPS3 was suppressed by Akt activation and Akt-mediated T70 phosphorylation, whereas after prolonged starvation, the protein levels of RPS3 notably increased, and abundant neuronal death occurred. These events coincided with ubiquitination and subsequent degradation of RPS3, controlled by HSP70 and the cochaperone E3 ligase: carboxy terminus of heat shock protein 70-interacting protein (CHIP). Thus, our study points to an extraribosomal role of RPS3 in balancing neuronal survival or death depending on the degree of starvation through CHIP-mediated polyubiquitination and degradation.

scholarly journals Principles of 60S ribosomal subunit assembly emerging from recent studies in yeast

2017 ◽  
Vol 474 (2) ◽  
pp. 195-214 ◽  
Author(s):  
Salini Konikkat ◽  
John L. Woolford,
Keyword(s):  
Ribosomal Rna ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Ribosomal Subunit ◽  
Ribosome Assembly ◽  
Small Nucleolar Rnas ◽  
Large Ribosomal Subunit ◽  
Yeast Saccharomyces Cerevisiae ◽  
Subunit Assembly ◽  
Nucleolar Rnas

Ribosome biogenesis requires the intertwined processes of folding, modification, and processing of ribosomal RNA, together with binding of ribosomal proteins. In eukaryotic cells, ribosome assembly begins in the nucleolus, continues in the nucleoplasm, and is not completed until after nascent particles are exported to the cytoplasm. The efficiency and fidelity of ribosome biogenesis are facilitated by >200 assembly factors and ∼76 different small nucleolar RNAs. The pathway is driven forward by numerous remodeling events to rearrange the ribonucleoprotein architecture of pre-ribosomes. Here, we describe principles of ribosome assembly that have emerged from recent studies of biogenesis of the large ribosomal subunit in the yeast Saccharomyces cerevisiae. We describe tools that have empowered investigations of ribosome biogenesis, and then summarize recent discoveries about each of the consecutive steps of subunit assembly.

scholarly journals Recent Advances on the Structure and Function of RNA Acetyltransferase Kre33/NAT10

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1035 ◽  
Author(s):  
Sophie Sleiman ◽  
Francois Dragon
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Ribosomal Subunit ◽  
40S Ribosomal Subunit ◽  
Functional Features ◽  
And Function ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome ◽  
Nucleolar Rna

Ribosome biogenesis is one of the most energy demanding processes in the cell. In eukaryotes, the main steps of this process occur in the nucleolus and include pre-ribosomal RNA (pre-rRNA) processing, post-transcriptional modifications, and assembly of many non-ribosomal factors and ribosomal proteins in order to form mature and functional ribosomes. In yeast and humans, the nucleolar RNA acetyltransferase Kre33/NAT10 participates in different maturation events, such as acetylation and processing of 18S rRNA, and assembly of the 40S ribosomal subunit. Here, we review the structural and functional features of Kre33/NAT10 RNA acetyltransferase, and we underscore the importance of this enzyme in ribosome biogenesis, as well as in acetylation of non-ribosomal targets. We also report on the role of human NAT10 in Hutchinson–Gilford progeria syndrome.

scholarly journals Distinct Mutations in Yeast TAFII25 Differentially Affect the Composition of TFIID and SAGA Complexes as Well as Global Gene Expression Patterns

2002 ◽  
Vol 22 (9) ◽  
pp. 3178-3193 ◽  
Author(s):  
Doris B. Kirschner ◽  
Elmar vom Baur ◽  
Christelle Thibault ◽  
Steven L. Sanders ◽  
Yann-Gaël Gangloff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Full Range ◽  
Expression Patterns ◽  
Cycle Phase ◽  
Gene Expression Patterns ◽  
Temperature Sensitive ◽  
Gene Promoters ◽  
M Cell ◽  
Phenotypic Changes

ABSTRACT The RNA polymerase II transcription factor TFIID, composed of the TATA-binding protein (TBP) and TBP-associated factors (TAFIIs), nucleates preinitiation complex formation at protein-coding gene promoters. SAGA, a second TAFII-containing multiprotein complex, is involved in transcription regulation in Saccharomyces cerevisiae. One of the essential protein components common to SAGA and TFIID is yTAFII25. We define a minimal evolutionarily conserved 91-amino-acid region of TAFII25 containing a histone fold domain that is necessary and sufficient for growth in vivo. Different temperature-sensitive mutations of yTAFII25 or chimeras with the human homologue TAFII30 arrested cell growth at either the G1 or G2/M cell cycle phase and displayed distinct phenotypic changes and gene expression patterns. Immunoprecipitation studies revealed that TAFII25 mutation-dependent gene expression and phenotypic changes correlated at least partially with the integrity of SAGA and TFIID. Genome-wide expression analysis revealed that the five TAFII25 temperature-sensitive mutant alleles individually affect the expression of between 18 and 33% of genes, whereas taken together they affect 64% of all class II genes. Thus, different yTAFII25 mutations induce distinct phenotypes and affect the regulation of different subsets of genes, demonstrating that no individual TAFII mutant allele reflects the full range of its normal functions.

scholarly journals Human Ribosomal Proteins RPeL27, RPeL43, and RPeL41 Are Upregulated in Nasopharyngeal Carcinoma Cell Lines

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Edmund Ui-Hang Sim ◽  
Stella Li-Li Chan ◽  
Kher-Lee Ng ◽  
Choon-Weng Lee ◽  
Kumaran Narayanan
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Ribosomal Protein ◽  
Cell Lines ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Expression Patterns ◽  
Transcript Level ◽  
Ribosomal Protein Genes ◽  
Significant Differential Expression ◽  
Protein Levels

Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes’ involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41, and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semiquantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than downregulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41, and RPeL43 as potential markers of NPC and provide insights into the interaction targets of RPeL27 and RPeL43 proteins.

scholarly journals Human PDCD2L Is an Export Substrate of CRM1 That Associates with 40S Ribosomal Subunit Precursors

2016 ◽  
Vol 36 (24) ◽  
pp. 3019-3032 ◽  
Author(s):  
Anne-Marie Landry-Voyer ◽  
Sarah Bilodeau ◽  
Danny Bergeron ◽  
Kiersten L. Dionne ◽  
Sarah A. Port ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Ribosome Biogenesis ◽  
Nuclear Export Signal ◽  
Ribosomal Subunit ◽  
Stable Complex ◽  
Dependent Manner ◽  
Reporter Protein ◽  
Ribosomal Subunits ◽  
40S Ribosomal Subunit ◽  
Late Maturation

Protein arginine methyltransferase 3 (PRMT3) forms a stable complex with 40S ribosomal protein S2 (RPS2) and contributes to ribosome biogenesis. However, the molecular mechanism by which PRMT3 influences ribosome biogenesis and/or function still remains unclear. Using quantitative proteomics, we identified human programmed cell death 2-like (PDCD2L) as a novel PRMT3-associated protein. Our data suggest that RPS2 promotes the formation of a conserved extraribosomal complex with PRMT3 and PDCD2L. We also show that PDCD2L associates with 40S subunit precursors that contain a 3′-extended form of the 18S rRNA (18S-E pre-rRNA) and several pre-40S maturation factors. PDCD2L shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner using a leucine-rich nuclear export signal that is sufficient to direct the export of a reporter protein. Although PDCD2L is not required for the biogenesis and export of 40S ribosomal subunits, we found that PDCD2L -null cells accumulate free 60S ribosomal subunits, which is indicative of a deficiency in 40S subunit availability. Our data also indicate that PDCD2L and its paralog, PDCD2, function redundantly in 40S ribosomal subunit production. Our findings uncover the existence of an extraribosomal complex consisting of PDCD2L, RPS2, and PRMT3 and support a role for PDCD2L in the late maturation of 40S ribosomal subunits.

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