The eukaryotic mRNA 5' cap structure facilitates translation. However, cap-
dependent translation is impaired at mitosis, suggesting a cap-independent
mechanism for mRNAs translated during mitosis. Translation of ornithine dec
arboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamine
s, peaks twice during the cell cycle, at the G1/S transition and at G2/M. H
ere, we describe a cap-independent internal ribosome entry site (IRES) in t
he ODC mRNA that functions exclusively at G2/M. This ensures elevated level
s of polyamines, which are implicated in mitotic spindle formation and chro
matin condensation. c-myc mRNA also contains an IRES that functions during
mitosis. Thus, IRES-dependent translation is likely to be a general mechani
sm to synthesize short-lived proteins even at mitosis, when cap-dependent t
ranslation is interdicted.