Premium
Nonsense Mediated Decay associated “Pioneer round of translation” could contribute to immune surveillance
Author(s) -
Schmidt Andreas,
Shastri Nilabh
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb68
Subject(s) - translation (biology) , microbiology and biotechnology , major histocompatibility complex , mutant , nonsense mediated decay , biology , immune system , mhc class i , antigen , peptide , gene , messenger rna , genetics , rna splicing , rna , biochemistry
Effectiveness of immune surveillance depends upon the display of peptides by MHC class I molecules (pMHC I) on the cell surface. Expression of pMHC I ensures that cytotoxic T cells can detect cells that are infected or transformed because virtually all proteins ‐ self, viral or mutant ‐ are processed to generate peptides. The peptides are derived mainly from newly synthesized proteins, which include defective translation products as well as those encoded in alternate translational reading frames. Here we tested the possibility that some antigenic peptides could also be derived from the “pioneer round of translation” that is associated with mechanisms of mRNA surveillance such as nonsense mediated decay (NMD). In HeLa cells siRNA mediated depletion of hUpf1, a key player in the NMD pathway inhibited the expression of MHC I molecules on the cell surface as did inhibition of total protein synthesis with the drug cyclohexamide. In contrast, inhibition of conventional protein synthesis with a dominant negative 4E BP mutant, did not affect generation of pMHC I. Furthermore, manipulation of NMD by altering the positioning of introns in antigen coding genes also influenced pMHC I expression in cells. Taken together our findings suggest that the NMD associated pioneer round of translation can contribute to antigenic peptides and thus to immune surveillance.