Bone marrow cells from patients with Shwachman-Diamond syndrome abnormally express genes involved in ribosome biogenesis and RNA processing.
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.
Cell Biology Program, Research Institute, University of Toronto, Toronto, Ontario, Canada.
Piya
P
Rujkijyanont
Sally-Lin
SL
Adams
Joseph
J
Beyene
Yigal
Y
Dror
D001854:Bone Marrow Cells / Q000378:metabolism*; D001855:Bone Marrow Diseases / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D010188:Exocrine Pancreatic Insufficiency / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome; D014158:Transcription, Genetic
D012269:Ribosomal Proteins; D012313:RNA