Integrated analyses of translatome and proteome identify the rules of translation selectivity in RPS14-deficient cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Haematologica Année : 2020

Integrated analyses of translatome and proteome identify the rules of translation selectivity in RPS14-deficient cells

Ismael Boussaid
  • Fonction : Auteur
Salomé Le Goff
  • Fonction : Auteur
Célia Floquet
  • Fonction : Auteur
Anna Raimbault
Pierre-Julien Viailly
  • Fonction : Auteur
Dina Al Dulaimi
  • Fonction : Auteur
Barbara Burroni
  • Fonction : Auteur
Isabelle Dusanter-Fourt
  • Fonction : Auteur
Patrick Mayeux
  • Fonction : Auteur
Bertrand Cosson
Michaela Fontenay

Résumé

In ribosomopathies, the Diamond-Blackfan anemia (DBA) or 5q- syndrome, ribosomal protein (RP) genes are affected by mutation or deletion, resulting in bone marrow erythroid hypoplasia. Unbalanced production of ribosomal subunits leading to a limited ribosome cellular content, regulates translation at the expense of the master erythroid transcription factor GATA1. In RPS14-deficient cells mimicking 5q- syndrome erythroid defects, we show that the transcript length, codon bias of the coding sequence (CDS) and 3'UTR structure are the key determinants of translation. In these cells, short transcripts with a structured 3'UTR and high CAI showed a decreased translation efficiency. Quantitative analysis of the whole proteome confirmed that the post-transcriptional changes depended on the transcript characteristics that governed the translation efficiency in conditions of low ribosome availability. In addition, proteins involved in normal erythroid differentiation share most determinants of translation selectivity. Our findings thus indicate that impaired erythroid maturation due to 5q- syndrome may proceed from a translational selectivity at the expense of the erythroid differentiation program and suggest that an interplay between the CDS and UTRs may regulate mRNA translation.

Dates et versions

hal-02571404 , version 1 (12-05-2020)

Identifiants

Citer

Ismael Boussaid, Salomé Le Goff, Célia Floquet, Emilie-Fleur Gautier, Anna Raimbault, et al.. Integrated analyses of translatome and proteome identify the rules of translation selectivity in RPS14-deficient cells. Haematologica, 2020, ⟨10.3324/haematol.2019.239970⟩. ⟨hal-02571404⟩
31 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More