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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...

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Autores principales: Mancini, Annalisa, Niemann-Seyde, Susanne C, Pankow, Rüdiger, El Bounkari, Omar, Klebba-Färber, Sabine, Koch, Alexandra, Jaworska, Ewa, Spooncer, Elaine, Gruber, Achim D, Whetton, Anthony D, Tamura, Teruko
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806247/
https://www.ncbi.nlm.nih.gov/pubmed/20051105
http://dx.doi.org/10.1186/1741-7007-8-1
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author Mancini, Annalisa
Niemann-Seyde, Susanne C
Pankow, Rüdiger
El Bounkari, Omar
Klebba-Färber, Sabine
Koch, Alexandra
Jaworska, Ewa
Spooncer, Elaine
Gruber, Achim D
Whetton, Anthony D
Tamura, Teruko
author_facet Mancini, Annalisa
Niemann-Seyde, Susanne C
Pankow, Rüdiger
El Bounkari, Omar
Klebba-Färber, Sabine
Koch, Alexandra
Jaworska, Ewa
Spooncer, Elaine
Gruber, Achim D
Whetton, Anthony D
Tamura, Teruko
author_sort Mancini, Annalisa
collection PubMed
description 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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spelling pubmed-28062472010-01-14 THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo Mancini, Annalisa Niemann-Seyde, Susanne C Pankow, Rüdiger El Bounkari, Omar Klebba-Färber, Sabine Koch, Alexandra Jaworska, Ewa Spooncer, Elaine Gruber, Achim D Whetton, Anthony D Tamura, Teruko BMC Biol Research article 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. BioMed Central 2010-01-05 /pmc/articles/PMC2806247/ /pubmed/20051105 http://dx.doi.org/10.1186/1741-7007-8-1 Text en Copyright ©2010 Mancini et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research article
Mancini, Annalisa
Niemann-Seyde, Susanne C
Pankow, Rüdiger
El Bounkari, Omar
Klebba-Färber, Sabine
Koch, Alexandra
Jaworska, Ewa
Spooncer, Elaine
Gruber, Achim D
Whetton, Anthony D
Tamura, Teruko
THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo
title THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo
title_full THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo
title_fullStr THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo
title_full_unstemmed THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo
title_short THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo
title_sort thoc5/fmip, an mrna export trex complex protein, is essential for hematopoietic primitive cell survival in vivo
topic Research article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806247/
https://www.ncbi.nlm.nih.gov/pubmed/20051105
http://dx.doi.org/10.1186/1741-7007-8-1
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