Evaluating Effects of HypomorphicThoc1Alleles on Embryonic Development inRb1Null Mice
The Rb1 tumor suppressor protein is a molecular adaptor that physically links transcription factors like E2f with various proteins acting on DNA or RNA to repress gene expression. Loss of Rb1 liberates E2f to activate the expression of genes mediating resulting phenotypes. Most Rb1 binding proteins, including E2f, interact through carboxyl-terminal protein interaction domains, but genetic evidence suggests that an amino-terminal protein interaction domain is also important. One protein that binds Rb1 through the amino-terminal domain is encoded byThoc1, a required component of the THO ribonucleoprotein complex important for RNA processing and transport. The physiological relevance of this interaction is unknown. Here we tested whetherThoc1mediates effects ofRb1loss on mouse embryonic development. We found thatThoc1deficiency delays embryo death, and this delay correlates with reduced apoptosis in the brain. E2f protein levels are reduced inRb1:Thoc1-deficient brain tissue. Expression of apoptotic regulatory genes regulated by E2f, like Apaf1 and Bak1, is also reduced. These observations suggest thatThoc1is required to support increased expression of E2f and apoptotic regulatory genes that trigger apoptosis uponRb1loss. These findings implicate Rb1 in the regulation of the THO ribonucleoprotein complex.