RP gene haploinsufficiency promotes extra sensory organ formation via a threshold effect

Translation of branched-chain aminotransferase-1 transcripts is impaired in cells haploinsufficient for ribosomal protein genes

Whole Genome Sequencing to Detect Small Deletions in Ribosomal Protein Genes in Diamond Blackfan Anemia Patients

Ribosomal Protein S24 Gene Is Mutated in Diamond-Blackfan Anemia

Recently we showed that de novo ribosome biosynthesis is transcriptionally regulated in Coccidia, depending on their life-cycle stage. Since the expression of ribosomal protein genes is likely coordinated, the transcriptional control of all Toxoplasma gondii ribosomal protein (RP) genes was analysed. Therefore, the complete set of all cytoplasmic RPs was defined, containing 79 different RPs in T. gondii. RP genes were randomly distributed over the genome, each with a unique upstream region with the exception of 8 RP genes which were paired in a head-to-head orientation. To study if the RP genes share conserved promoter elements, a database was made containing upstream sequences of all T. gondii RP genes. Promoter activity was confirmed for the upstream sequences of 8 RP genes, some of which are comparable in strength to the alpha-tubulin promoter. In the complete set of RP upstream sequences 2 novel and highly conserved elements were identified, named Toxoplasma Ribosomal Protein (TRP)-1 (consensus: TCGGCTTATATTCGG) and TRP-2 ([T/C]GCATGC[G/A]). TRP-1 and/or TRP-2 were present in 95% of all RP upstream sequences and moreover, were specifically localized in a small region near the presumptive transcriptional start site (10-330 bp upstream). Although TRP elements were mostly absent in known T. gondii promoters, they are present elsewhere in the T. gondii genome suggesting that they operate not only in RP genes but in a larger set of genes. The identification of TRP elements creates a basis to further study the underlying mechanism by which RP transcription is controlled in T. gondii.

Polyclonal somatic gene rescue via uniparental disomy confers multilineage hematopoietic potential in treatment-independent patients with DBA syndrome

SNP Array Genotyping Reveals Constitutional and Mosaic Losses of Ribosomal Protein Gene Regions In Patients with Diamond Blackfan Anemia without Ribosomal Protein Gene Mutations.

Ribosomal protein (RP) genes encode structural components of ribosomes, the cellular machinery for protein synthesis. A single functional copy has been maintained in most of 78–80 RP families in animals due to evolutionary constraints imposed by gene dosage balance. Some fungal species have maintained duplicate copies in most RP families. The mechanisms by which the RP genes were duplicated and maintained and their functional significance are poorly understood. To address these questions, we identified all RP genes from 295 fungi and inferred the timing and nature of gene duplication events for all RP families. We found that massive duplications of RP genes have independently occurred by different mechanisms in three distantly related lineages: budding yeasts, fission yeasts, and Mucoromycota. The RP gene duplicates in budding yeasts and Mucoromycota were mainly created by whole genome duplication events. However, duplicate RP genes in fission yeasts were likely generated by retroposition, which is unexpected considering their dosage sensitivity. The sequences of most RP paralogs have been homogenized by repeated gene conversion in each species, demonstrating parallel concerted evolution, which might have facilitated the retention of their duplicates. Transcriptomic data suggest that the duplication and retention of RP genes increased their transcript abundance. Physiological data indicate that increased ribosome biogenesis allowed these organisms to rapidly consume sugars through fermentation while maintaining high growth rates, providing selective advantages to these species in sugar-rich environments.

High Frequency of Large Gene Deletions Detected by Multiplex Ligation-Dependent Probe Amplification in Diamond Blackfan Anemia,

Translational machinery of channel catfish: I. A transcriptomic approach to the analysis of 32 40S ribosomal protein genes and their expression

Yeast cells modulate their protein synthesis capacity in response to physiological needs through the transcriptional control of ribosomal protein (RP) genes. Here we demonstrate that the transcription factor Sfp1, previously shown to play a role in the control of cell size, regulates RP gene expression in response to nutrients and stress. Under optimal growth conditions, Sfp1 is localized to the nucleus, bound to the promoters of RP genes, and helps promote RP gene expression. In response to inhibition of target of rapamycin (TOR) signaling, stress, or changes in nutrient availability, Sfp1 is released from RP gene promoters and leaves the nucleus, and RP gene transcription is down-regulated. Additionally, cells lacking Sfp1 fail to appropriately modulate RP gene expression in response to environmental cues. We conclude that Sfp1 integrates information from nutrient- and stress-responsive signaling pathways to help control RP gene expression.

Analysis of Ribosomal Protein Genes Associated with Diamond Blackfan Anemia (DBA) In German DBA Patients and Their Relatives

Shwachman-Diamond Syndrome (SDS) is a multi-system genetic disorder with bone marrow failure. SBDS, the gene associated with SDS, has been postulated to play a role in ribosome biogenesis and RNA processing, but its functions are still unknown. To study whether these pathways are interrupted when Sbds protein is lost, we studied the expression of related genes in patient SBDS-/- cells by an oligonucleotide microarray. We first analysed ribosomal protein (RP) genes, which are normally co-regulated. In SDS, 27 of the 85 RP genes were downregulated. Among the downregulated RP genes, seven are known to be associated with the inhibition of apoptosis. RPS27L, which mediates p53-dependent induction of apoptosis, was the only upregulated RP gene. Interestingly, several genes involved in RP mRNA transcription were downregulated without affecting the expression of genes involved in mRNA degradation, suggesting that the downregulation of the RP gene expression might be at the transcriptional level. Importantly we also found dysregulation of multiple genes involved in rRNA transcription and pre-rRNA processing. We conclude that SDS marrow cells exhibit major dysregulation of RP, RNA processing and RNA transcription genes.

Ribosome is one of the most abundant organelles in all living cells and plays a crucial role in cell growth. Synthesis of ribosomal components is tightly related with the change of growth conditions. We have comparatively analyzed the 5’ flanking region of ribosomal protein (RP) genes in Arabidopsis and O. sativa. In both Arabidopsis and O. sativa, there are two putative transcriptional factor binding motifs (telo box and site II elements) overrepresented in the proximal promoter region with a strong positional bias in most of the RP genes, which suggests the conserved mechanism of transcription-level control in RP genes of these two organisms. Tri-nucleotide repeats motif CTT and CCG were also common in 5’ flanking region of RP genes in Arabidopsis and O. sativa. However, we only found CCG repeat motif was enriched in O. sativa RP genes and most of them were clustered in the 5’ UTR region. This finding reveals molecular mechanism for divergent regulation of RP genes in Arabidopsis and O. sativa, and gives the possible clue to the mechanism of controlling O. sativa RP genes expression at the translation level.

Isolation and characterization of medaka ribosomal protein S3a ( fte-1) cDNA and gene

Target Enrichment and High-Throughput Sequencing of 80 Ribosomal Protein Genes to Identify Mutations Associated with Diamond-Blackfan Anaemia.