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Open Access Research article

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

Annalisa Mancini15, Susanne C Niemann-Seyde1, Rüdiger Pankow2, Omar El Bounkari1, Sabine Klebba-Färber1, Alexandra Koch1, Ewa Jaworska3, Elaine Spooncer3, Achim D Gruber4, Anthony D Whetton3 and Teruko Tamura1*

Author affiliations

1 Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany

2 Abteilung Molekulare Genetik, Forschungsinstitut fuer Molekulare Pharmakologie, Krahmerstr. 6, D-12207 Berlin, Germany

3 Stem Cell and Leukemia Proteomics Laboratory, Manchester Academic Health Sciences Centre, University of Manchester, Christie Hospital, Manchester M20 4BX, UK

4 Institute of Veterinary Pathology, Freie Universitaet Berlin, Robert-von-Ostertag- Str. 15, D-14163 Berlin, Germany

5 Developmental and Regenerative Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA

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Citation and License

BMC Biology 2010, 8:1  doi:10.1186/1741-7007-8-1

Published: 5 January 2010

Abstract

Background

The 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.

Results

To 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.

Conclusion

THOC5/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.