Translation termination-dependent deadenylation of MYC mRNA in human cells
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Béatrice Jolles1, Affaf Aliouat1, Vérène Stierlé1, Samia Salhi1 and Olivier Jean-Jean1
1Sorbonne Université, CNRS-UMR8256, Biological Adaptation and Ageing, Institut de Biologie Paris Seine (B2A-IBPS), F-75252 Paris, France
Olivier Jean-Jean, email: [email protected]
Keywords: MYC; mRNA deadenylation; poly(A) tail; translation termination; eRF3
Received: June 21, 2017 Accepted: May 08, 2018 Published: May 25, 2018
The earliest step in the mRNA degradation process is deadenylation, a progressive shortening of the mRNA poly(A) tail by deadenylases. The question of when deadenylation takes place remains open. MYC mRNA is one of the rare examples for which it was proposed a shortening of the poly(A) tail during ongoing translation. In this study, we analyzed the poly(A) tail length distribution of various mRNAs, including MYC mRNA. The mRNAs were isolated from the polysomal fractions of polysome profiling experiments and analyzed using ligase-mediated poly(A) test analysis. We show that, for all the mRNAs tested with the only exception of MYC, the poly(A) tail length distribution does not change in accordance with the number of ribosomes carried by the mRNA. Conversely, for MYC mRNA, we observed a poly(A) tail length decrease in the fractions containing the largest polysomes. Because the fractions with the highest number of ribosomes are also those for which translation termination is more frequent, we analyzed the poly(A) tail length distribution in polysomal fractions of cells depleted in translation termination factor eRF3. Our results show that the shortening of MYC mRNA poly(A) tail is alleviated by the silencing of translation termination factor eRF3. These findings suggest that MYC mRNA is co-translationally deadenylated and that the deadenylation process requires translation termination to proceed.
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