Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class i pathway

Sébastien Apcher, Guy Millot, Chrysoula Daskalogianni, Alexander Scherl, Bénédicte Manoury, Robin Fahraeus

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

86 Citations (Scopus)

Résumé

The scanning of maturing mRNAs by ribosomes plays a key role in the mRNA quality control process. When ribosomes first engage with the newly synthesized mRNA, and if peptides are produced, is unclear, however. Here we show that ribosomal scanning of prespliced mRNAs occurs in the nuclear compartment, and that this event produces peptide substrates for the MHC class I pathway. Inserting antigenic peptide sequences in introns that are spliced out before the mRNAs exit the nuclear compartment results in an equal amount of antigenic peptide products as when the peptides are encoded from the main open reading frame (ORF). Taken together with the detection of intron-encoded nascent peptides and RPS6/RPL7-carrying complexes in the perinucleolar compartment, these results show that peptides are produced by a translation event occurring before mRNA splicing. This suggests that ribosomes occupy and scan mRNAs early in the mRNA maturation process, and suggests a physiological role for nuclear mRNA translation, and also helps explain how the immune system tolerates peptides derived from tissue-specific mRNA splice variants.

langue originaleAnglais
Pages (de - à)17951-17956
Nombre de pages6
journalProceedings of the National Academy of Sciences of the United States of America
Volume110
Numéro de publication44
Les DOIs
étatPublié - 29 oct. 2013
Modification externeOui

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