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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
10:00

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

Translational upregulation of the X-linked inhibitor of apoptosis

Martin Holcik1

  • 1Solange Gauthier Karsh Molecular Genetics Laboratory, Department of Pediatrics, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, K1H 8L1 Canada. martin@mgcheo.med.uottawa.ca

Annals of the New York Academy of Sciences
|March 23, 2004
PubMed

Insights

The X-linked inhibitor of apoptosis protein (XIAP) is a key regulator of programmed cell death. Its translation is controlled by a unique internal ribosome entry site (IRES), allowing XIAP synthesis during cellular stress.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The X-linked inhibitor of apoptosis protein (XIAP) is a potent intrinsic regulator of programmed cell death.
  • XIAP's critical role in apoptosis necessitates complex regulatory mechanisms.
  • XIAP synthesis is selectively regulated, in addition to its functional regulation.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling XIAP synthesis.
  • To elucidate the role of internal ribosome entry site (IRES) in XIAP translation.
  • To understand how XIAP translation is modulated during cellular stress.

Main Methods:

  • Analysis of XIAP mRNA 5' untranslated region for regulatory elements.
  • Investigating cap-independent translation initiation.
  • Studying XIAP mRNA translation under conditions of cellular stress.

Main Results:

  • A unique internal ribosome entry site (IRES) was identified in the 5' untranslated region of XIAP mRNA.
  • This IRES mediates cap-independent translation initiation of XIAP.
  • XIAP mRNA is actively translated via the IRES during cellular stress, when global protein synthesis is inhibited.

Conclusions:

  • The IRES-mediated translation of XIAP is a critical mechanism for regulating apoptosis.
  • This regulatory pathway allows for selective synthesis of XIAP during cellular stress.
  • Understanding XIAP IRES regulation provides insights into controlling programmed cell death.

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