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


CONCLUSIONS
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.
Mancini
Annalisa
A
Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str, 1, D-30623 Hannover, Germany. annalisa_mancini@hotmail.de
Niemann-Seyde
Susanne C
SC
Pankow
Rüdiger
R
El Bounkari
Omar
O
Klebba-Färber
Sabine
S
Koch
Alexandra
A
Jaworska
Ewa
E
Spooncer
Elaine
E
Gruber
Achim D
AD
Whetton
Anthony D
AD
Tamura
Teruko
T
D000740:Anemia / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001773:Blood Cells / Q000502:physiology; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000502:physiology; D007970:Leukopenia / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; C402364:Fmip protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C511176:Thoc1 protein, mouse