title: PSF controls expression of histone variants and cellular viability in thymocytes.
abstract: Even with the availability of tissue-restricted knockouts, studying the role of essential, multifunctional proteins in vivo is often complicated by the complete loss of cell viability. Here we make use of a knock-down approach to investigate the function of the essential protein PSF (polypyrimidine tract binding protein-associated splicing factor) in thymocytes. PSF is an RNA- and DNA-binding protein that has roles in all aspects of RNA biogenesis from transcription to stability. We show that a 50% reduction in expression of PSF in the thymus leads to an increase in apoptosis and a corresponding decrease in thymic cellularity. Using microarrays we find that thymocytes depleted of PSF show reduced expression of several histone genes relative to wildtype littermates likely due to reduced mRNA stability. Remarkably, reduced expression of a specific one of these histone genes (H2AE from histone cluster 1) is sufficient to induce apoptosis of a cultured T cell line. Therefore, we conclude that PSF contributes to the stability of a subset of histone genes and that loss of H2AE expression in the PSF-deficient thymocytes uniquely contributes to an increase in thymic apoptosis.
authors: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 422 Curie Blvd., Philadelphia, PA 19104-6059, USA. florian.heyd@uni-marburg.de
authors: Florian
authors: F
authors: Heyd
authors: Kristen W
authors: KW
authors: Lynch
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D055785:Gene Knockdown Techniques; D006657:Histones / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D000072670:PTB-Associated Splicing Factor; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
chemical_list: D006657:Histones; D000072670:PTB-Associated Splicing Factor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins