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

2.50
Hdl Handle:
http://hdl.handle.net/10541/109347
Title:
THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo.
Authors:
Mancini, Annalisa; Niemann-Seyde, Susanne C; Pankow, Rüdiger; El Bounkari, Omar; Klebba-Faerber, Sabine; Koch, Alexandra; Jaworska, Ewa; Spooncer, Elaine; Gruber, Achim D; Whetton, Anthony D; Tamura, Teruko
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.
Affiliation:
Institut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str, 1, D-30623 Hannover, Germany. annalisa_mancini@hotmail.de
Citation:
THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo. 2010, 8:1 BMC Biol.
Journal:
BMC Biology
Issue Date:
2010
URI:
http://hdl.handle.net/10541/109347
DOI:
10.1186/1741-7007-8-1
PubMed ID:
20051105
Type:
Article
Language:
en
ISSN:
1741-7007
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMancini, Annalisaen
dc.contributor.authorNiemann-Seyde, Susanne Cen
dc.contributor.authorPankow, Rüdigeren
dc.contributor.authorEl Bounkari, Omaren
dc.contributor.authorKlebba-Faerber, Sabineen
dc.contributor.authorKoch, Alexandraen
dc.contributor.authorJaworska, Ewaen
dc.contributor.authorSpooncer, Elaineen
dc.contributor.authorGruber, Achim Den
dc.contributor.authorWhetton, Anthony Den
dc.contributor.authorTamura, Terukoen
dc.date.accessioned2010-08-09T16:17:53Z-
dc.date.available2010-08-09T16:17:53Z-
dc.date.issued2010-
dc.identifier.citationTHOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo. 2010, 8:1 BMC Biol.en
dc.identifier.issn1741-7007-
dc.identifier.pmid20051105-
dc.identifier.doi10.1186/1741-7007-8-1-
dc.identifier.urihttp://hdl.handle.net/10541/109347-
dc.description.abstractBACKGROUND: 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.en
dc.language.isoenen
dc.subjectAnaemiaen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnemia-
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshBlood Cells-
dc.subject.meshBone Marrow Cells-
dc.subject.meshBone Marrow Transplantation-
dc.subject.meshCell Survival-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHepatocytes-
dc.subject.meshIntracellular Signaling Peptides and Proteins-
dc.subject.meshLeukocytes-
dc.subject.meshLeukopenia-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Knockout-
dc.subject.meshRNA, Messenger-
dc.subject.meshRNA-Binding Proteins-
dc.titleTHOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo.en
dc.typeArticleen
dc.contributor.departmentInstitut fuer Biochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str, 1, D-30623 Hannover, Germany. annalisa_mancini@hotmail.deen
dc.identifier.journalBMC Biologyen

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