A cell cycle-dependent internal ribosome entry site.
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 decarboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamines, peaks twice during the cell cycle, at the G1/S transition and at G2/M. Here, we describe a cap-independent internal ribosome entry site (IRES) in the ODC mRNA that functions exclusively at G2/M. This ensures elevated levels of polyamines, which are implicated in mitotic spindle formation and chromatin condensation. c-myc mRNA also contains an IRES that functions during mitosis. Thus, IRES-dependent translation is likely to be a general mechanism to synthesize short-lived proteins even at mitosis, when cap-dependent translation is interdicted.
Pyronnet
S
S
Department of Biochemistry and McGill Cancer Center, McGill University, Montréal, Qúebec, Canada.
Pradayrol
L
L
Sonenberg
N
N
D020121:5' Untranslated Regions; D018387:Codon, Initiator; D004790:Enzyme Induction / Q000187:drug effects; D016193:G1 Phase / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000502:physiology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D010849:Picornaviridae / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012315:RNA Caps; D020123:Sirolimus / Q000494:pharmacology
D020121:5' Untranslated Regions; D018387:Codon, Initiator; D016271:Proto-Oncogene Proteins c-myc; D012315:RNA Caps; D009955:Ornithine Decarboxylase; D020123:Sirolimus