RB1 5́UTR contains an IRES related to cell cycle control and cancer progression

Abstract

Retinoblastoma gene1 (RB1) is the first tumor suppressor gene that stands as the guardian of the gate of the G1 period and plays a central role in proliferation and differentiation. However, no reports focused on the possible internal ribosome entry site (IRES) function of the RB1 gene flanking sequence. In this study, we constructed a bicistronic reporter with the RB1 5′untranslated region (5́UTR) inserted between two reporter coding regions. We found RB1 5′UTR harbors an IRES and has higher activity in cancer cell lines than normal cells. Besides, RB1 IRES acquired the highest activity in the G0/G1 phase of the cell cycle, and the RB1 5′UTR mutation collected from retinoblastoma decreased IRES activity compared with RB1 5′UTR wild-type. These data indicated that RB1 IRES is a mechanism of stress regulation and is related to cell cycle control and cancer progression.