Abstract
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.
Highlights
The co-transcriptional packaging of nascent RNA transcripts into RNP complexes is important for transcription, RNA processing, and RNA export from the nucleus [1]
We have examined whether CD150+ hematopoietic stem cells (HSC) and CD1502 multipotent progenitor cells (MPP) cells that precede the myeloid/lymphoid bifurcation are affected by Thoc1 loss
The data presented indicate that Thoc1 deficiency can have both cell autonomous and non-cell autonomous effects on hematopoiesis in the adult mouse, and the effects observed are dependent on cell lineage
Summary
The co-transcriptional packaging of nascent RNA transcripts into RNP complexes is important for transcription, RNA processing, and RNA export from the nucleus [1]. Potential combinatorial permutations are vast enough to facilitate unique RNP processing pathways for different subsets of transcripts [2] These observations have inspired the hypothesis that co- and post-transcriptional RNP mediated mechanisms support the elaboration of coordinated gene expression [3,4]. While the importance of RNP mediated mechanisms for gene expression and genome integrity is increasingly appreciated, the contribution of individual RNP complexes to normal growth and development in mammals is not well characterized. Identifying these contributions will further the understanding of how defects in RNP mediated processes lead to disease [6]
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