Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation

P Singh1, L Wedeken, L C Waters

  • 1Institute for Biochemistry, Westfälische-Wilhelms-Universität Münster, Münster, Germany.

Oncogene
|June 7, 2011
PubMed

Insights

Programmed cell death protein 4 (Pdcd4) directly suppresses translation of c-myb mRNA. Its N-terminal domain targets Pdcd4 to specific RNA sequences, revealing a novel mechanism in gene regulation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • Programmed cell death protein 4 (Pdcd4) is a tumor suppressor involved in transcription and translation.
  • Pdcd4's cytoplasmic role in suppressing translation of structured mRNAs is known, but target mRNAs and recruitment mechanisms remain unclear.

Purpose of the Study:

  • To identify the first natural messenger RNA (mRNA) target of Pdcd4.
  • To elucidate the mechanisms by which Pdcd4 targets specific mRNAs for translational suppression.

Main Methods:

  • Identification of c-myb mRNA as a Pdcd4 target.
  • Analysis of Pdcd4's translational suppression of c-myb mRNA.
  • Investigation of the role of Pdcd4's N-terminal domain in RNA binding and targeting.

Main Results:

  • c-myb mRNA is identified as the first natural translational target of Pdcd4.
  • Pdcd4-mediated translational suppression of c-myb mRNA depends on coding region sequences.
  • Pdcd4's N-terminal domain is crucial for targeting Pdcd4 to c-myb RNA via preferential binding.

Conclusions:

  • Pdcd4 directly suppresses the translation of a natural mRNA (c-myb).
  • The N-terminal domain of Pdcd4 plays a key role in targeting it to specific mRNAs.
  • This study reveals a novel mechanism for Pdcd4-mediated gene regulation at the translational level.

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