scholarly journals A Molecular Titration System Coordinates Ribosomal Protein Gene Transcription with Ribosomal RNA Synthesis

2016 ◽  
Vol 64 (4) ◽  
pp. 720-733 ◽  
Author(s):  
Benjamin Albert ◽  
Britta Knight ◽  
Jason Merwin ◽  
Victoria Martin ◽  
Diana Ottoz ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Gene Transcription ◽  
Ribosomal Rna ◽  
Rna Synthesis ◽  
Protein Gene ◽  
Ribosomal Protein Gene ◽  
Titration System ◽  
Molecular Titration

scholarly journals Two distinct promoter architectures centered on dynamic nucleosomes control ribosomal protein gene transcription

2014 ◽  
Vol 28 (15) ◽  
pp. 1695-1709 ◽  
Author(s):  
Britta Knight ◽  
Slawomir Kubik ◽  
Bhaswar Ghosh ◽  
Maria Jessica Bruzzone ◽  
Marcel Geertz ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Gene Transcription ◽  
Protein Gene ◽  
Ribosomal Protein Gene

De Novo RPS20 Mutations in Diamond Blackfan Anemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2667-2667 ◽  
Author(s):  
Saleh Bhar ◽  
Lisa Mirabello ◽  
Nimrat Chatterjee ◽  
Christopher Williams ◽  
Blanche P. Alter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ribosomal Protein ◽  
Exome Sequencing ◽  
Ribosomal Rna ◽  
Congenital Anomalies ◽  
Protein Gene ◽  
De Novo ◽  
Ribosomal Protein Gene ◽  
Diamond Blackfan Anemia ◽  
Whole Exome

Abstract Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by pure red blood cell aplasia, variable congenital anomalies and increased risk of malignancy. Approximately 50-60% of cases are due to germline, heterozygous mutations in 1 of 13 genes that encode components of either the small (RPS7, RPS10, RPS17, RPS19, RPS24, RPS26 and RPS29) or large (RPL5, RPL11, RPL15, RPL26, RPL31 and RPL35A) ribosomal subunits. The mutations may be either inherited or de novo. Consistent with DBA being a ribosomopathy, defects in ribosome assembly, altered ribosomal RNA processing and nucleolar stress are observed in cells of patients with DBA and ribosomal protein gene mutations. Mutations in GATA1, a hematopoietic transcription factor, have also been reported in rare X-linked recessive cases. Whole exome sequencing was independently carried out on two white/Hispanic probands with genetically uncharacterized DBA (BMF92 and NCI-62-1). Both presented with transfusion-dependent anemia during the first week of life. Bone marrow evaluations revealed marked erythroid hypoplasia characteristic of DBA. One of the probands (BMF92) experienced a spontaneous remission of his anemia toward the end of the first year of life, possibly related to corticosteroids administered for bronchiolitis. Subsequently, his erythrocyte adenosine deaminase(eADA) level was measured and elevated [10.5 units (mol/min/gm hg); reference range 0.42-3.5 units]. BMF92’s hypoplastic anemia later recurred and was found to be steroid refractory. NCI-62-1 is a male, now 12 years of age and red cell transfusion dependent. BMF92 and NCI-62-1 are of normal stature and have no documented congenital anomalies, although both have experienced chronic colitis. In both cases, family history for DBA was negative and parental eADA levels were within normal limits. Whole exome sequencing of peripheral blood DNA, validated by Sanger or Ion Torrent targeted sequencing, identified heterozygous variants of unknown significance in the ribosomal protein gene RPS20. Parental studies revealed both variants to be de novo. The variants were mutated at the same genomic position, but resulted in different amino acid substitutions in RPS20 [hg19 chr8 56985758, c.251A>T, p.I84N (BMF92) and 56985758, c.251A>C, p.I84S (NCI-62-1)]. Buccal swab analysis performed in BMF92 confirmed the presence of the variant. Both variants were novel, based on inspection of several databases, including dbSNP, 1000 Genomes, NHLBI Exome Sequencing Project, clinical WES data at the Whole Genome Laboratory at Baylor College of Medicine, Kaviar, Human Genome Mutation Database and ClinVar, totally well over 10,000 individuals as well as the COSMIC database, which reports somatic mutations in cancer. In silicoanalyses were consistent with the variants being damaging and disease causing (PolyPhen-2, SIFT and Mutation Taster), affecting highly evolutionarily conserved residues (GERP, PhyloP and Sitewise likelihood-ratio score) and decreasing the stability of the protein structure (MUpro and I-Mutant2.0). The above data strongly suggest that the RPS20 variants in these cases are disease causing. A recent report implicated a germline RPS20 truncating mutation in a four-generation pedigree with familial nonpolyposis colorectal carcinoma; however, the mutation carriers were reported to not manifest features of DBA (Nieminen et al., Gastroenterology 2014). This raises the likelihood of allele-specific effects. Functional assays of our probands’ mutations, including quantification of RPS20 protein and ribosomal RNA precursor steady state levels in patient versus control lymphoblastoid cell lines as well as analysis of the impact of mutant RPS20 protein expression on p53 and downstream targets are underway to determine their contribution to the DBA phenotype. Disclosures No relevant conflicts of interest to declare.

Splicing control of the L1 ribosomal protein gene of X. laevis: structural similarities between sequences present in the regulatory intron and in the 28S ribosomal RNA

1990 ◽  
Vol 14 (2-3) ◽  
pp. 111-112 ◽  
Author(s):  
P. Fragapane ◽  
E. Caffarelli ◽  
B. Santoro ◽  
S. Sperandio ◽  
M. Lener ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Ribosomal Rna ◽  
Protein Gene ◽  
Ribosomal Protein Gene
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