THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo

BMC Biology

Research Article

Rüdiger Pankow¹  Sabine Klebba-Färber²  Alexandra Koch²  Susanne C Niemann-Seyde²  Omar El Bounkari²  Teruko Tamura²  Annalisa Mancini³  Achim D Gruber⁴  Ewa Jaworska⁵  Elaine Spooncer⁵  Anthony D Whetton⁵ 

[1] Abteilung Molekulare Genetik, Forschungsinstitut fuer Molekulare Pharmakologie, Krahmerstr. 6, D-12207, Berlin, Germany;Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623, Hannover, Germany;Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623, Hannover, Germany;Developmental and Regenerative Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, 10029, New York, NY, USA;Institute of Veterinary Pathology, Freie Universitaet Berlin, Robert-von-Ostertag- Str. 15, D-14163, Berlin, Germany;Stem Cell and Leukemia Proteomics Laboratory, Manchester Academic Health Sciences Centre, University of Manchester, Christie Hospital, M20 4BX, Manchester, UK;

关键词: Bone Marrow Cell;    Nuclear Export;    mRNA Export;    Bone Marrow Cell Transplantation;    Normal Bone Marrow Cell;   

DOI  :  10.1186/1741-7007-8-1

 received in 2009-06-22, accepted in 2010-01-05,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe transcription/export complex is evolutionarily conserved from yeast to man and is required for coupled transcription elongation and nuclear export of mRNAs. FMIP(Fms interacting protein) is a member of the THO (suppressors of the transcriptional defects of hpr1delta by overexpression) complex which is a subcomplex of the transcription/export complex. THO complex (THOC) components are not essential for bulk poly (A)+ RNA export in higher eukaryotes, but for the nuclear export of subset of mRNAs, however, their exact role is still unclear.ResultsTo study the role of THOC5/Fms interacting protein in vivo, we generated THOC5/Fms interacting protein knockout mice. Since these mice are embryonic lethal, we then generated interferon inducible conditional THOC5/Fms interacting protein knockout mice. After three poly injections all of the mice died within 14 days. No pathological alterations, however, were observed in liver, kidney or heart. Thus we considered the hematopoietic system and found that seven days after poly injection, the number of blood cells in peripheral blood decreased drastically. Investigation of bone marrow cells showed that these became apoptotic within seven days after poly injection. Committed myeloid progenitor cells and cells with long term reconstituting potential were lost from bone marrow within four days after poly injection. Furthermore, infusion of normal bone marrow cells rescued mice from death induced by loss of THOC5/Fms interacting protein.ConclusionTHOC5/Fms interacting protein is an essential element in the maintenance of hematopoiesis. Furthermore, mechanistically depletion of THOC5/Fms interacting protein causes the down-regulation of its direct interacting partner, THOC1 which may contribute to altered THO complex function and cell death.

【 授权许可】

Unknown   
© Mancini et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.