raf Regulates the Postnatal Repression of the Mouse α-Fetoprotein Gene at the Posttranscriptional Level

Abstract

The mouse a-fetoprotein (AFP) gene is transcribed at a high rate in liver during the second half of gestation. Its steady-state mRNA levels decrease 10⁴-fold shortly after birth, at least in part as the consequence of a dramatic decrease in its transcription rate. The final basal level of AFP mRNA in adult liver is influenced by a trans-acting locus on chromosome 15 termed raf. Two strategies were used to demonstrate that the raf gene acts posttranscriptionally to affect the processing and/or stability of AFP transcripts. Transgenic mouse studies demonstrated that raf gene action is independent of both positive and negative transcription control elements of the AFP gene. Nuclear run-on analysis was used to confirm that transcriptions of both AFP transgenes and another endogenous ra/-responsive gene, H19, are invariant with respect to the raf genotype. Thus, the postnatal repression of the AFP gene is mediated by both transcriptional and posttranscriptional mechanisms.