The Shwachman-Bodian-Diamond syndrome associated protein interacts with HsNip7 and its down-regulation affects gene expression at the transcriptional and translational levels
- Center for Structural Molecular Biology, Brazilian Synchrotron Light Laboratory, LNLS Rua Giuseppe Maximo Scolfaro 10000, PO Box 6192, CEP 13084-971, Campinas, SP (Brazil)
- Department of Biochemistry, Institute of Chemistry, University of Sao Paulo Av. Prof. Lineu Prestes 748, Sao Paulo, SP 05508-900 (Brazil)
- Department of Microbiology, Immunology and Parasitology, Federal University of Sao Paulo Rua Botucatu 862, Sao Paulo, SP 04023-062 (Brazil)
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.
- OSTI ID:
- 21045914
- Journal Information:
- Experimental Cell Research, Vol. 313, Issue 20; Other Information: DOI: 10.1016/j.yexcr.2007.06.024; PII: S0014-4827(07)00314-X; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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