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A cell cycle-dependent internal ribosome entry site.

S Pyronnet1, L Pradayrol, N Sonenberg

  • 1Department of Biochemistry and McGill Cancer Center, McGill University, Montréal, Qúebec, Canada.

Molecular Cell
|July 6, 2000
PubMed
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During mitosis, cap-dependent translation is impaired. Ornithine decarboxylase mRNA uses a cap-independent internal ribosome entry site (IRES) to ensure polyamine synthesis for cell division.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Eukaryotic mRNA 5' cap structure typically facilitates translation.
  • Cap-dependent translation is impaired during mitosis.
  • A cap-independent mechanism is necessary for mRNA translation during mitosis.

Purpose of the Study:

  • To investigate the mechanism of ornithine decarboxylase (ODC) mRNA translation during mitosis.
  • To identify and characterize a potential cap-independent translation element in ODC mRNA.
  • To understand the role of polyamines in mitosis.

Main Methods:

  • Analysis of ODC mRNA sequence for regulatory elements.
  • Functional assays to test for internal ribosome entry site (IRES) activity.
  • Cell cycle synchronization and analysis of ODC and polyamine levels.

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Main Results:

  • A functional internal ribosome entry site (IRES) was identified in the ODC mRNA.
  • This ODC IRES functions exclusively during the G2/M phase of the cell cycle.
  • Elevated polyamine levels, crucial for mitosis, are maintained by IRES-dependent ODC translation.

Conclusions:

  • ODC mRNA utilizes a cap-independent IRES for translation during mitosis.
  • IRES-dependent translation ensures the synthesis of essential proteins like ODC when cap-dependent translation is inhibited.
  • This mechanism is likely a general strategy for synthesizing short-lived proteins during mitosis, as exemplified by c-myc mRNA also containing a mitotic IRES.