Search for UV-responsive genes in human cells by differential mRNA display: involvement of human ras-related GTP-binding protein, Rheb, in UV susceptibility.

The search for genes responsible for the sensitivity of human cells to cell-killing effects of UV is an important area of biological research. To identify candidate genes responsible for UV sensitization, levels of mRNA expression were compared between UV-sensitive RSa cells and UV-resistant variant UV(r)-1 cells, using a differential display method and Northern blot analysis. Messenger RNA expression levels of human Ras homologue enriched in brain (Rheb) and/or a Rheb-like gene were up-regulated and slightly decreased in UV-irradiated RSa and UV(r)-1 cells, compared to in mock-irradiated cells, respectively. RSa and UV(r)-1 cells, both of which were treated with antisense oligonucleotides for Rheb RNA, exhibited an increased resistance to UV cell-killing. It remains unclear why UV(r)-1 cells are resistant to UV yet express Rheb mRNA at high levels. However, the results of antisense experiments together with the up-regulation in UV-irradiated RSa cells, suggest that Rheb is involved in the UV sensitization of both cells to UV cell-killing.