THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival <it>in vivo</it>
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-01-01
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| Series: | BMC Biology |
| Online Access: | http://www.biomedcentral.com/1741-7007/8/1 |
| _version_ | 1828533544768503808 |
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| author | Spooncer Elaine Jaworska Ewa Koch Alexandra Klebba-Färber Sabine El Bounkari Omar Pankow Rüdiger Niemann-Seyde Susanne C Mancini Annalisa Gruber Achim D Whetton Anthony D Tamura Teruko |
| author_facet | Spooncer Elaine Jaworska Ewa Koch Alexandra Klebba-Färber Sabine El Bounkari Omar Pankow Rüdiger Niemann-Seyde Susanne C Mancini Annalisa Gruber Achim D Whetton Anthony D Tamura Teruko |
| author_sort | Spooncer Elaine |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>To study the role of THOC5/Fms interacting protein <it>in vivo</it>, 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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-11T23:11:41Z |
| format | Article |
| id | doaj.art-4c4ca940be334111868791e2145b33fa |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-11T23:11:41Z |
| publishDate | 2010-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-4c4ca940be334111868791e2145b33fa2022-12-22T00:46:40ZengBMCBMC Biology1741-70072010-01-0181110.1186/1741-7007-8-1THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival <it>in vivo</it>Spooncer ElaineJaworska EwaKoch AlexandraKlebba-Färber SabineEl Bounkari OmarPankow RüdigerNiemann-Seyde Susanne CMancini AnnalisaGruber Achim DWhetton Anthony DTamura Teruko<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>To study the role of THOC5/Fms interacting protein <it>in vivo</it>, 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.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1741-7007/8/1 |
| spellingShingle | Spooncer Elaine Jaworska Ewa Koch Alexandra Klebba-Färber Sabine El Bounkari Omar Pankow Rüdiger Niemann-Seyde Susanne C Mancini Annalisa Gruber Achim D Whetton Anthony D Tamura Teruko THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival <it>in vivo</it> BMC Biology |
| title | THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival <it>in vivo</it> |
| title_full | THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival <it>in vivo</it> |
| title_fullStr | THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival <it>in vivo</it> |
| title_full_unstemmed | THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival <it>in vivo</it> |
| title_short | THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival <it>in vivo</it> |
| title_sort | thoc5 fmip an mrna export trex complex protein is essential for hematopoietic primitive cell survival it in vivo it |
| url | http://www.biomedcentral.com/1741-7007/8/1 |
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