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

Mancini A, Niemann-Seyde SC, Pankow R, El Bounkari O, Klebba-Färber S, Koch A, Jaworska E, Spooncer E, Gruber AD, Whetton AD, Tamura T - BMC Biol. (2010)

Bottom Line: Thus we considered the hematopoietic system and found that seven days after poly injection, the number of blood cells in peripheral blood decreased drastically.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str, 1, D-30623 Hannover, Germany. annalisa_mancini@hotmail.de

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.

Show MeSH
THOC5/FMIP expression is reduced in specific organs. (A, B) 250 μg of poly (I:C) were injected into six-week-old Mx-cre THOC5/FMIP (flox/flox) (n = 8) or control THOC5/FMIP (flox/flox) (n = 6) mice three times at two-to-three-day intervals. THOC5/FMIP protein levels in liver, bone marrow, spleen (A), testicles, lung, kidney, large intestine, and heart (B) were examined by THOC5/FMIP specific immunoblotting. Proteins were extracted from each organ. Total protein amount was standardized by actin specific immunoblotting.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2806247&req=5

Figure 2: THOC5/FMIP expression is reduced in specific organs. (A, B) 250 μg of poly (I:C) were injected into six-week-old Mx-cre THOC5/FMIP (flox/flox) (n = 8) or control THOC5/FMIP (flox/flox) (n = 6) mice three times at two-to-three-day intervals. THOC5/FMIP protein levels in liver, bone marrow, spleen (A), testicles, lung, kidney, large intestine, and heart (B) were examined by THOC5/FMIP specific immunoblotting. Proteins were extracted from each organ. Total protein amount was standardized by actin specific immunoblotting.

Mentions: We examined, therefore, the THOC5/FMIP protein level in liver, spleen, kidney, lung, intestine, testicles and bone marrow using THOC5/FMIP specific antibody and western blot [16]. After poly (I:C) injection, the level of THOC5/FMIP is reduced by approximately 80% in liver (P < 0.0001), kidney (P = 0.001), heart (P < 0.0001) and bone marrow (P < 0.0001) within seven days in all Mx-cre THOC5/FMIP (flox/flox) mice. In contrast, in spleen, intestine, testes and lung, the level is not reduced (Figure 2A and 2B).


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

Mancini A, Niemann-Seyde SC, Pankow R, El Bounkari O, Klebba-Färber S, Koch A, Jaworska E, Spooncer E, Gruber AD, Whetton AD, Tamura T - BMC Biol. (2010)

THOC5/FMIP expression is reduced in specific organs. (A, B) 250 μg of poly (I:C) were injected into six-week-old Mx-cre THOC5/FMIP (flox/flox) (n = 8) or control THOC5/FMIP (flox/flox) (n = 6) mice three times at two-to-three-day intervals. THOC5/FMIP protein levels in liver, bone marrow, spleen (A), testicles, lung, kidney, large intestine, and heart (B) were examined by THOC5/FMIP specific immunoblotting. Proteins were extracted from each organ. Total protein amount was standardized by actin specific immunoblotting.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806247&req=5

Figure 2: THOC5/FMIP expression is reduced in specific organs. (A, B) 250 μg of poly (I:C) were injected into six-week-old Mx-cre THOC5/FMIP (flox/flox) (n = 8) or control THOC5/FMIP (flox/flox) (n = 6) mice three times at two-to-three-day intervals. THOC5/FMIP protein levels in liver, bone marrow, spleen (A), testicles, lung, kidney, large intestine, and heart (B) were examined by THOC5/FMIP specific immunoblotting. Proteins were extracted from each organ. Total protein amount was standardized by actin specific immunoblotting.
Mentions: We examined, therefore, the THOC5/FMIP protein level in liver, spleen, kidney, lung, intestine, testicles and bone marrow using THOC5/FMIP specific antibody and western blot [16]. After poly (I:C) injection, the level of THOC5/FMIP is reduced by approximately 80% in liver (P < 0.0001), kidney (P = 0.001), heart (P < 0.0001) and bone marrow (P < 0.0001) within seven days in all Mx-cre THOC5/FMIP (flox/flox) mice. In contrast, in spleen, intestine, testes and lung, the level is not reduced (Figure 2A and 2B).

Bottom Line: Thus we considered the hematopoietic system and found that seven days after poly injection, the number of blood cells in peripheral blood decreased drastically.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str, 1, D-30623 Hannover, Germany. annalisa_mancini@hotmail.de

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.

Show MeSH