scholarly journals Defective Ribosomal Protein Gene Expression Alters Transcription, Translation, Apoptosis, and Oncogenic Pathways in Diamond-Blackfan Anemia

Stem Cells ◽  
2006 ◽  
Vol 24 (9) ◽  
pp. 2034-2044 ◽  
Author(s):  
Hanna T. Gazda ◽  
Alvin T. Kho ◽  
Despina Sanoudou ◽  
Jan M. Zaucha ◽  
Isaac S. Kohane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ribosomal Protein ◽  
Protein Gene ◽  
Ribosomal Protein Gene ◽  
Diamond Blackfan Anemia ◽  
Oncogenic Pathways

Association of RAP1 binding sites with stringent control of ribosomal protein gene transcription in Saccharomyces cerevisiae

1991 ◽  
Vol 11 (5) ◽  
pp. 2723-2735 ◽  
Author(s):  
C M Moehle ◽  
A G Hinnebusch
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Ribosomal Protein ◽  
Binding Sites ◽  
Protein Gene ◽  
Ribosomal Protein Gene ◽  
Ribosomal Protein Genes ◽  
Biosynthetic Genes ◽  
Stringent Control

An amino acid limitation in bacteria elicits a global response, called stringent control, that leads to reduced synthesis of rRNA and ribosomal proteins and increased expression of amino acid biosynthetic operons. We have used the antimetabolite 3-amino-1,2,4-triazole to cause histidine limitation as a means to elicit the stringent response in the yeast Saccharomyces cerevisiae. Fusions of the yeast ribosomal protein genes RPL16A, CRY1, RPS16A, and RPL25 with the Escherichia coli lacZ gene were used to show that the expression of these genes is reduced by a factor of 2 to 5 during histidine-limited exponential growth and that this regulation occurs at the level of transcription. Stringent regulation of the four yeast ribosomal protein genes was shown to be associated with a nucleotide sequence, known as the UASrpg (upstream activating sequence for ribosomal protein genes), that binds the transcriptional regulatory protein RAP1. The RAP1 binding sites also appeared to mediate the greater ribosomal protein gene expression observed in cells growing exponentially than in cells in stationary phase. Although expression of the ribosomal protein genes was reduced in response to histidine limitation, the level of RAP1 DNA-binding activity in cell extracts was unaffected. Yeast strains bearing a mutation in any one of the genes GCN1 to GCN4 are defective in derepression of amino acid biosynthetic genes in 10 different pathways under conditions of histidine limitation. These Gcn- mutants showed wild-type regulation of ribosomal protein gene expression, which suggests that separate regulatory pathways exist in S. cerevisiae for the derepression of amino acid biosynthetic genes and the repression of ribosomal protein genes in response to amino acid starvation.

scholarly journals Ribosomal protein gene deletions in Diamond-Blackfan anemia

Blood ◽  
2011 ◽  
Vol 118 (26) ◽  
pp. 6943-6951 ◽  
Author(s):  
Jason E. Farrar ◽  
Adrianna Vlachos ◽  
Eva Atsidaftos ◽  
Hannah Carlson-Donohoe ◽  
Thomas C. Markello ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Ribosomal Proteins ◽  
Protein Gene ◽  
Single Nucleotide Polymorphism Array ◽  
Ribosomal Protein Gene ◽  
Small Subunit ◽  
Ribosomal Protein Genes ◽  
Gene Deletions ◽  
Diamond Blackfan Anemia ◽  
Genome Wide

Abstract Diamond-Blackfan anemia (DBA) is a congenital BM failure syndrome characterized by hypoproliferative anemia, associated physical abnormalities, and a predisposition to cancer. Perturbations of the ribosome appear to be critically important in DBA; alterations in 9 different ribosomal protein genes have been identified in multiple unrelated families, along with rarer abnormalities of additional ribosomal proteins. However, at present, only 50% to 60% of patients have an identifiable genetic lesion by ribosomal protein gene sequencing. Using genome-wide single-nucleotide polymorphism array to evaluate for regions of recurrent copy variation, we identified deletions at known DBA-related ribosomal protein gene loci in 17% (9 of 51) of patients without an identifiable mutation, including RPS19, RPS17, RPS26, and RPL35A. No recurrent regions of copy variation at novel loci were identified. Because RPS17 is a duplicated gene with 4 copies in a diploid genome, we demonstrate haploinsufficient RPS17 expression and a small subunit ribosomal RNA processing abnormality in patients harboring RPS17 deletions. Finally, we report the novel identification of variable mosaic loss involving known DBA gene regions in 3 patients from 2 kindreds. These data suggest that ribosomal protein gene deletion is more common than previously suspected and should be considered a component of the initial genetic evaluation in cases of suspected DBA.

scholarly journals MYSM1 maintains ribosomal protein gene expression in hematopoietic stem cells to prevent hematopoietic dysfunction

JCI Insight ◽  
2020 ◽  
Vol 5 (13) ◽  
Author(s):  
Jad I. Belle ◽  
HanChen Wang ◽  
Amanda Fiore ◽  
Jessica C. Petrov ◽  
Yun Hsiao Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Ribosomal Protein ◽  
Protein Gene ◽  
Ribosomal Protein Gene ◽  
Hematopoietic Stem

Coordinated Changes in Classes of Ribosomal Protein Gene Expression Is Associated with Light-Induced Retinal Degeneration

2004 ◽  
Vol 45 (11) ◽  
pp. 3885 ◽  
Author(s):  
Ruby Grewal ◽  
Jadwiga Stepczynski ◽  
Rhonda Kelln ◽  
Timothy Erickson ◽  
Ruth Darrow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ribosomal Protein ◽  
Retinal Degeneration ◽  
Protein Gene ◽  
Ribosomal Protein Gene
Sign in / Sign up

Export Citation Format

Share Document