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Different mechanisms preserve translation of programmed cell death 8 and JunB in virus-infected endothelial cells

Huimiao Jiang1, Hansjörg Schwertz, Douglas I Schmid

  • 1Division of Vascular Surgery, University of Utah, Salt Lake City, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|February 14, 2012
PubMed
Abstract

Insights

Stressful conditions like poliovirus infection halt most cap-dependent translation in endothelial cells. However, some messenger RNAs (mRNAs) utilize internal ribosome entry sites (IRES) for continued protein production, revealing alternative translation pathways.

Area of Science:

  • Molecular Biology
  • Virology
  • Cell Biology

Background:

  • Eukaryotic mRNA translation typically relies on cap-dependent ribosome scanning.
  • Internal ribosome entry sites (IRES) allow for cap-independent translation initiation.
  • The role of IRES-mediated translation in stressed primary human endothelial cells (ECs) was previously unknown.

Purpose of the Study:

  • To investigate whether IRES-mediated translation occurs in stressed primary human endothelial cells.
  • To identify specific mRNAs that are translated via IRES during stress conditions.

Main Methods:

  • Microarray analysis of polyribosomal mRNA from poliovirus (PV)-infected ECs.
  • Confirmation of cap-dependent translation inhibition by assessing eukaryotic initiation factor (eIF) 4G cleavage and protein synthesis.
  • Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for validating microarray data.
  • Dicistronic analysis to confirm the presence and function of IRES elements.

Main Results:

  • PV infection significantly reduced cap-dependent translation, with 87.4% of mRNAs dissociating from polysomes.
  • Twelve percent of mRNAs remained polysome-associated, and 0.6% were significantly enriched.
  • Programmed cell death 8 (PDCD8) and JunB mRNAs showed enriched polysome association and increased protein expression.
  • IRES elements were confirmed in the 5' untranslated region of PDCD8 mRNA, but not JunB mRNA.

Conclusions:

  • Microarray profiling of polyribosomal mRNA in PV-infected ECs can identify mRNAs with preserved translation during stress.
  • Internal ribosome entry is a mechanism for privileged translation under stress-induced cap-dependent initiation cessation.
  • Other mechanisms, beyond IRES, may also contribute to maintaining translation under cellular stress.

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