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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-10, Vol.110 (44), p.17951-17956
Main Authors: Apcher, Sébastien, Millot, Guy, Daskalogianni, Chrysoula, Scherl, Alexander, Manoury, Bénédicte, Fåhraeus, Robin
Format: Article
Language:English
Subjects:
Antibodies
Antigen presentation
Biological Sciences
Cell Line
Cell Nucleus - immunology
Cytoplasm
Epitopes
Exons
Histocompatibility Antigens Class I - immunology
Humans
immune system
Introns
Mass Spectrometry
Maturation
Messenger RNA
open reading frames
Peptides
Peptides - immunology
Peptides - metabolism
process control
Protein Biosynthesis - immunology
quality control
Real-Time Polymerase Chain Reaction
rev genes
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
ribosomes
Ribosomes - immunology
Ribosomes - metabolism
RNA
RNA, Messenger - metabolism
Signal Transduction - immunology
T lymphocytes
translation (genetics)
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1309956110