Publikationsdatenbank

THOC5/FMIP, an mRNA Export TREX Complex Protein, is essential for Hematopoietic Primitive Cell Survival in vivo (2010)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Mancini, Annalisa

Niemann-Seyde, Susanne C

Pankow, Rüdiger

El Bounkari, Omar

Klebba-Färber, Sabine

Koch, Alexandra

Jaworska, Ewa

Spooncer, Elaine

Gruber, Achim D

Whetton, Anthony D

Tamura, Teruko

Quelle

BMC biology

Bandzählung: 8

Heftzählung: Art. 1

Seiten: 17 S.

ISSN: 1741-7007

Sprache

Englisch

Verweise

DOI: 10.1186/1741-7007-8-1

Pubmed: 20051105

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.

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.

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.