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

Proceedings of the National Academy of Sciences of the United States of America
Sébastien ApcherRobin Fåhraeus

Abstract

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.

References

Nov 1, 1991·European Journal of Immunology·O RötzschkeH G Rammensee
Dec 7, 1989·Nature·M L Zapp, M R Green
Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·P G CoulieT Boon
Dec 5, 1998·The Journal of Biological Chemistry·P AskjaerJ Kjems
Oct 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S KhanM Groettrup
Feb 28, 2002·Annual Review of Immunology·Nilabh ShastriThomas Serwold
Dec 3, 1955·Nature·V G ALLFREY, A E MIRSKY
May 6, 2004·Journal of Cell Science·Tominori KimuraJun-Ichi Fujisawa
May 18, 2004·Nature Immunology·Antoine PerchelletJoan Goverman
Sep 14, 2004·Nature Structural & Molecular Biology·Fabrice LejeuneLynne E Maquat
Mar 14, 2007·Annual Review of Biochemistry·Yao-Fu ChangMiles F Wilkinson
Oct 2, 2008·The Journal of Biological Chemistry·Kristine O'BrienMelissa J Moore
Nov 15, 2008·Nature Chemical Biology·Matthew D Disney
Oct 19, 2010·Nature Structural & Molecular Biology·Matthew D DaughertyAlan D Frankel
Nov 5, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brian P DolanJonathan W Yewdell
Mar 11, 2011·Cellular and Molecular Life Sciences : CMLS·Shelley R Starck, Nilabh Shastri
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sebastien ApcherRobin Fåhraeus
Apr 5, 2012·The Journal of Cell Biology·Alexandre DavidJonathan W Yewdell
Nov 20, 2012·Nature Chemical Biology·Sarah A SlavoffAlan Saghatelian
Jan 2, 2013·Journal of Proteomics·Florent GluckAlexander Scherl
Jan 10, 2013·Annual Review of Immunology·Janice S BlumPeter Cresswell
May 15, 2013·Histochemistry and Cell Biology·Douglas J Taatjes, Jürgen Roth

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Citations

Apr 2, 2014·Médecine sciences : M/S·Emilie DuvalletSébastien Apcher
Apr 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Dmitry BourdetskyArie Admon
Sep 30, 2014·Trends in Molecular Medicine·Vincent P Mauro, Stephen A Chappell
Oct 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jonathan W Yewdell, Alexandre David
May 17, 2015·Molecular Immunology·Sebastien ApcherRobin Fåhraeus
Dec 20, 2015·Trends in Plant Science·Roger P HellensRichard C Macknight
Jul 29, 2015·Biochimie·Sheeba RasheediNasreen Z Ehtesham
Feb 28, 2015·Tissue Antigens·C HermannL H Boyle
Jan 2, 2015·Current Opinion in Immunology·Rafael J ArgüelloPhilippe Pierre
Feb 22, 2014·Current Opinion in Immunology·Nilabh ShastriTakayuki Kanaseki
Aug 12, 2014·Biochemical Society Transactions·Tina McLeodSaverio Brogna
Dec 4, 2014·Current Opinion in Immunology·Diana P GranadosClaude Perreault
Mar 17, 2015·Current Opinion in Immunology·Sebastian Springer
May 13, 2015·Current Opinion in Immunology·Nilabh Shastri, Jonathan W Yewdell
Apr 1, 2014·Cell·Hosung JungChristine E Holt
Dec 9, 2014·Nucleus·Sabyasachi Baboo, Peter R Cook
Apr 22, 2016·Current Opinion in Immunology·Christopher C Norbury
Mar 21, 2015·Science·Maximilian W Popp, Lynne E Maquat
Apr 23, 2016·Current Opinion in Immunology·Sébastien ApcherRobin Fåhraeus
Dec 28, 2016·Cell Research·Rong-Fu Wang, Helen Y Wang
Apr 8, 2017·Nature Medicine·Jiajie Wei, Jonathan W Yewdell
May 28, 2017·The International Journal of Biochemistry & Cell Biology·Rodrigo Prado Martins, Robin Fåhraeus
May 3, 2014·Therapeutic Advances in Vaccines·Joseph D Comber, Ramila Philip
Apr 2, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jiajie WeiJonathan W Yewdell
Dec 29, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amy L PalmerBrian P Dolan
Jul 18, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heather D HickmanJonathan W Yewdell
Jan 10, 2019·Nucleic Acids Research·Rodrigo Prado MartinsRobin Fåhraeus
Nov 16, 2013·Nature Chemical Biology·Petra Van Damme, Gerben Menschaert
Aug 22, 2017·Cellular and Molecular Life Sciences : CMLS·Céline M Laumont, Claude Perreault
Aug 2, 2017·Annual Review of Cell and Developmental Biology·Serge PlazaFrançois Payre
Jul 26, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hadas Weinstein-MaromGideon Gross
Nov 15, 2016·The Journal of Clinical Investigation·Hillary PearsonClaude Perreault
Nov 21, 2018·Virologica Sinica·Jiajie Wei, Jonathan W Yewdell
May 17, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Damien J ZankerWeisan Chen
May 24, 2017·Cell & Bioscience·Andrew NicklessZhongsheng You
Nov 15, 2016·The Journal of Clinical Investigation·Devin Dersh, Jonathan W Yewdell
Mar 27, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ning YangJonathan W Yewdell
Aug 21, 2020·Nature Reviews. Immunology·Devin DershJonathan W Yewdell
Sep 15, 2020·Oncoimmunology·Mathilde BoulpicanteSébastien Apcher
May 22, 2020·Computational and Structural Biotechnology Journal·Ranen Aviner
Oct 31, 2019·Trends in Cell Biology·Jonathan W YewdellRobin Fåhraeus
Feb 11, 2021·Biomolecules·Paolo Cascio

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