Translation termination-dependent deadenylation of MYC mRNA in human cells

Béatrice Jolles1, Affaf Aliouat1, Vérène Stierlé1

  • 1Sorbonne Université, CNRS-UMR8256, Biological Adaptation and Ageing, Institut de Biologie Paris Seine (B2A-IBPS), F-75252 Paris, France.

Oncotarget
|June 15, 2018
PubMed

Insights

MYC mRNA undergoes deadenylation during translation, a process linked to translation termination. Silencing translation termination factor eRF3 alleviates this MYC mRNA poly(A) tail shortening.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Gene Regulation

Background:

  • Deadenylation, the shortening of the mRNA poly(A) tail, initiates mRNA degradation.
  • The timing of deadenylation, particularly during active translation, remains largely uncharacterized.
  • MYC mRNA has been suggested to undergo poly(A) tail shortening while translation is still in progress.

Purpose of the Study:

  • To investigate the temporal relationship between mRNA translation and deadenylation.
  • To determine if MYC mRNA exhibits co-translational deadenylation.
  • To elucidate the role of translation termination in MYC mRNA deadenylation.

Main Methods:

  • Polysome profiling to isolate mRNAs based on ribosome occupancy.
  • Ligase-mediated poly(A) test analysis to measure poly(A) tail length.
  • Analysis of poly(A) tail length in MYC mRNA from polysomal fractions.
  • Assessment of MYC mRNA deadenylation in cells with depleted translation termination factor eRF3.

Main Results:

  • For most mRNAs, poly(A) tail length distribution was independent of ribosome number.
  • MYC mRNA showed decreased poly(A) tail length in fractions with higher ribosome counts.
  • Depletion of translation termination factor eRF3 reduced the shortening of the MYC mRNA poly(A) tail.

Conclusions:

  • MYC mRNA is subject to co-translational deadenylation.
  • Translation termination is a required step for MYC mRNA deadenylation.
  • These findings provide new insights into the regulation of MYC mRNA stability and expression.

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