The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse.
Co-transcriptionally assembled ribonucleoprotein (RNP) complexes are critical for RNA processing and nuclear export. RNPs have been hypothesized to contribute to the regulation of coordinated gene expression, and defects in RNP biogenesis contribute to genome instability and disease. Despite the large number of RNPs and the importance of the molecular processes they mediate, the requirements for individual RNP complexes in mammalian development and tissue homeostasis are not well characterized. THO is an evolutionarily conserved, nuclear RNP complex that physically links nascent transcripts with the nuclear export apparatus. THO is essential for early mouse embryonic development, limiting characterization of the requirements for THO in adult tissues. To address this shortcoming, a mouse strain has been generated allowing inducible deletion of the Thoc1 gene which encodes an essential protein subunit of THO. Bone marrow reconstitution was used to generate mice in which Thoc1 deletion could be induced specifically in the hematopoietic system. We find that granulocyte macrophage progenitors have a cell autonomous requirement for Thoc1 to maintain cell growth and viability. Lymphoid lineages are not detectably affected by Thoc1 loss under the homeostatic conditions tested. Myeloid lineages may be more sensitive to Thoc1 loss due to their relatively high rate of proliferation and turnover.
Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
Laura
L
Pitzonka
Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
Sumana
S
Ullas
Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
Meenalakshmi
M
Chinnam
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
Benjamin J
BJ
Povinelli
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
Daniel T
DT
Fisher
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
Michelle
M
Golding
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
Michelle M
MM
Appenheimer
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
Michael J
MJ
Nemeth
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
Sharon
S
Evans
Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
David W
DW
Goodrich
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006098:Granulocytes / Q000166:cytology; D006706:Homeostasis; D016130:Immunophenotyping; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023461:Myeloid Progenitor Cells / Q000166:cytology*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C511176:Thoc1 protein, mouse