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Abstract
Accumulating evidence suggests that regulation of RNA processing through an RNP-driven mechanism is important for coordinated gene expression. This hypothesis predicts that defects in RNP biogenesis will adversely affect the elaboration of specific gene expression programs. To explore the role of RNP biogenesis on mammalian development, we have characterized the phenotype of mice hypomorphic for Thoc1. Thoc1 encodes an essential component of the evolutionarily conserved TREX complex. TREX accompanies the elongating RNA polymerase II and facilitates RNP assembly and recruitment of RNA processing factors. Hypomorphic Thoc1 mice are viable despite significantly reduced Thoc1 expression in the tissues examined. While most tissues of Thoc1-deficient mice appear to develop and function normally, gametogenesis is severely compromised. Male infertility is associated with a loss in spermatocyte viability and abnormal endocrine signaling. We suggest that loss of spermatocyte viability is a consequence of defects in the expression of genes required for normal differentiation of cell types within the testes. A number of the genes affected appear to be direct targets for regulation by Thoc1. These findings support the notion that Thoc1-mediated RNP assembly contributes to the coordinated expression of genes necessary for normal differentiation and development in vivo.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://mcb.asm.org/ .
ACKNOWLEDGMENTS
The paper is dedicated to the memory of our colleague Peter Moens.
We thank members of the Goodrich and Moens labs for helpful discussions and critical insight.
This work was supported by NCI grant CA125665 (to D.W.G.). NCI Cancer Center Support Grant CA016056 supported the Cell Analysis, Transgenic Mouse, and Gene Expression Core facilities used in this work. The Vanderbilt Hormone Assay & Analytical Services Core is supported in part by NIH grant U24 DK59637.