IMMORTALIZATION OF RAT EMBRYO FIBROBLASTS BY A 3'-UNTRANSLATED REGION

We have exploited a cross species expression screen to search for cell ular immortalizing activities. A newt blastemal cDNA expression librar y was transfected into rat embryo fibroblasts and immortal cell lines were selected. This identified a 1-kb cDNA fragment which has a low re presentation in the cDNA library and is derived from the 3'-UTR of an alpha-glucosidase-related mRNA. Expression of this sequence in rat emb ryo fibroblasts has shown that it is active in promoting colony format ion and immortalization. It is also able to cooperate with an immortal ization-defective deletion mutant of SV40 T antigen, indicating that i t can exert its growth-stimulatory activity in the pathway activated b y a viral immortalizing oncogene. This is the first example of an immo rtalizing activity mediated by an RNA sequence, and further analysis o f its mechanism should provide new insights into senescence and immort alization. (C) 1998 Academic Press.