The Shwachman-Bodian-Diamond syndrome associated protein interacts with HsNip7 and its down-regulation affects gene expression at the transcriptional and translational levels.
The Shwachman-Bodian-Diamond syndrome (SDS) is an autosomal disorder with pleiotropic phenotypes including pancreatic, skeletal and bone marrow deficiencies and predisposition to hematological dysfunctions. SDS has been associated to mutations in the SBDS gene, encoding a highly conserved protein that was shown to function in ribosome biogenesis in yeast. In this work, we show that SBDS is found in complexes containing the human Nip7 ortholog. Analysis of pre-rRNA processing in a stable SBDS knock-down HEK293-derivative cell line revealed accumulation of a small RNA which is a further indication of SBDS involvement in rRNA biosynthesis. Global transcription and polysome-bound mRNA profiling revealed that SBDS knock-down affects expression of critical genes involved in brain development and function, bone morphogenesis, blood cell proliferation and differentiation, and cell adhesion. Expression of a group of growth and signal transduction factors and of DNA damage response genes is also affected. In SBDS knock-down cells, 34 mRNAs showed decreased and 55 mRNAs showed increased association to polysomes, among which is a group encoding proteins involved in alternative splicing and RNA modification. These results indicate that SBDS is required for accurate expression of genes important for proper brain, skeletal, and blood cell development.
Hesling
Cédric
C
Center for Structural Molecular Biology, Brazilian Synchrotron Light Laboratory, LNLS Rua Giuseppe Maximo Scolfaro 10000, PO Box 6192, CEP 13084-971, Campinas, SP, Brazil.
Oliveira
Carla C
CC
Castilho
Beatriz A
BA
Zanchin
Nilson I T
NI
D002460:Cell Line; D002499:Centrifugation, Density Gradient; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011132:Polyribosomes / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
C499553:NIP7 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C470521:SBDS protein, human