TRANSCRIPTION OF UNR ((U)UNDER-BAR-PSTREAM OF (N)UNDER-BAR-(R)UNDER-BAR-AS) DOWN-MODULATES N-RAS EXPRESSION IN-VIVO

The ras proteins (Harvey, Kirsten and S-ras) are kev regulators of sig nal transduction and a perturbation of their GDP/GTP cycle is frequent ly observed in tumors, In mammals, N-ras constitutes with unr (upstrea m of N-ras) a tightly linked tandem of ubiquitously expressed genes, A lthough unr and N-ras appear to be involved in distinct functions, thi s unusual genetic organization could be important for the regulation o f N-ras expression, Specifically, transcription of unr could negativel y regulate that of N-ras by transcriptional interference, To investiga te this possibility, we have deleted the unr promoter by homologous re combination in murine embryonic stem cells, Analysis of tissues of het erozygous mice revealed an increase in N-ras mRNA accumulation ranging between 20 and 65%, in agreement rrith the suppression of a transcrip tional interference, (C) 1997 Federation of European Biochemical Socie ties.