The 5'-UTR of DDB2 harbors an IRES element and upregulates translation during stress conditions

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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

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Wenyan Dai1, Wennan Ma1, Qi Li1

  • 1School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province 214122, PR China.

Gene
|July 19, 2015
PubMed

Insights

The study found that the 5' untranslated region (UTR) of DDB2 contains an internal ribosome entry site (IRES) element. This DDB2 IRES activity is enhanced under stress conditions, revealing a new mechanism for regulating this tumor suppressor.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • DDB2 is a tumor suppressor involved in DNA repair (Nucleotide Excision Repair) and apoptosis.
  • DDB2 translation levels increase during serum starvation.
  • The role of 5'-UTR elements in DDB2 gene expression was unclear.

Purpose of the Study:

  • To investigate if the DDB2 5'-UTR contains an internal ribosome entry site (IRES) element.
  • To characterize the DDB2 IRES activity and its regulation under stress conditions.

Main Methods:

  • Utilized a bicistronic luciferase reporter assay to test for IRES activity.
  • Inserted the DDB2 5'-UTR between two reporter genes.
  • Employed Mfold for secondary structure prediction.
  • Performed deletion analysis of the 5'-UTR to identify key regions for IRES function.

Main Results:

  • Demonstrated that the DDB2 5'-UTR possesses IRES activity, initiating cap-independent translation.
  • Predicted a stable secondary structure for the DDB2 5'-UTR.
  • Identified the full-length 5'-UTR as crucial for optimal IRES activity.
  • Showed that DDB2 IRES activity is enhanced under cellular stress conditions.

Conclusions:

  • The DDB2 5'-UTR contains a functional IRES element.
  • Stress conditions promote DDB2 IRES activity, suggesting a novel regulatory mechanism.
  • This finding contributes to understanding DDB2 expression control in DNA damage response pathways.
Keywords:
DDB2IRES activityInternal ribosome entry segmentTranslation

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