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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.

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Deletion of THOC5/FMIP is lethal in adult mice. Three day- (n = 25) (A) and nine-week-old (n = 7) (B) mice were injected with 50, and 500 μg of poly (I:C), respectively. Injection was performed i.p. three times at two to three day intervals. (arrows: poly (I:C) injection).
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Figure 3: Deletion of THOC5/FMIP is lethal in adult mice. Three day- (n = 25) (A) and nine-week-old (n = 7) (B) mice were injected with 50, and 500 μg of poly (I:C), respectively. Injection was performed i.p. three times at two to three day intervals. (arrows: poly (I:C) injection).

Mentions: Since conventional knockout mice died at the embryonic stage, we determined whether THOC5/FMIP is necessary for postnatal mouse survival. We therefore injected three-day-old mice (n = 25) with 50 μg of poly (I:C) three times at two-to-three-day intervals. Mx-cre THOC5/FMIP(flox/flox) mice began dying three days after injection and then all died within 14 days after the first injection, whereas all control mice (THOC5/FMIP(flox/flox)) survived (Figure 3A). We then injected 500 μg of poly (I:C) into nine-week-old mice (n = 7) three times over a two-to-three-day interval. These mice began dying eight days after the first poly (I:C) injection and all of them were dead within 14 days (Figure 3B), indicating that THOC5/FMIP gene expression is essential for the survival of adult mice.


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)

Deletion of THOC5/FMIP is lethal in adult mice. Three day- (n = 25) (A) and nine-week-old (n = 7) (B) mice were injected with 50, and 500 μg of poly (I:C), respectively. Injection was performed i.p. three times at two to three day intervals. (arrows: poly (I:C) injection).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Deletion of THOC5/FMIP is lethal in adult mice. Three day- (n = 25) (A) and nine-week-old (n = 7) (B) mice were injected with 50, and 500 μg of poly (I:C), respectively. Injection was performed i.p. three times at two to three day intervals. (arrows: poly (I:C) injection).
Mentions: Since conventional knockout mice died at the embryonic stage, we determined whether THOC5/FMIP is necessary for postnatal mouse survival. We therefore injected three-day-old mice (n = 25) with 50 μg of poly (I:C) three times at two-to-three-day intervals. Mx-cre THOC5/FMIP(flox/flox) mice began dying three days after injection and then all died within 14 days after the first injection, whereas all control mice (THOC5/FMIP(flox/flox)) survived (Figure 3A). We then injected 500 μg of poly (I:C) into nine-week-old mice (n = 7) three times over a two-to-three-day interval. These mice began dying eight days after the first poly (I:C) injection and all of them were dead within 14 days (Figure 3B), indicating that THOC5/FMIP gene expression is essential for the survival of adult mice.

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