A Single-nucleotide Deletion Leads to Rapid Degradation ofTAP-1mRNA in a Melanoma Cell Line

Tianyu Yang, Beth A. McNally, Soldano Ferrone, Yang Liu, Pan Zheng
2003 Journal of Biological Chemistry  
Both viruses and tumors evade cytotoxic T lymphocyte-mediated host immunity by down-regulation of antigen presentation machineries. This can be achieved by either down-regulation of transcription of antigen presentation genes or posttranslational inactivation of proteins involved in antigen presentation. In this study, a major histocompatibility complex (MHC) class I-deficient melanoma cell line, SK-MEL-19, was found deficient in the expression of the transporter associated with antigen
more » ... ith antigen processing (TAP)-1 mRNA even after IFN-␥ stimulation, despite its active transcription of the TAP-1 gene. This abnormality was caused by a single-nucleotide deletion at position ؉1489 of the TAP-1 gene and was corrected by cycloheximide, which inhibits RNA degradation. Using an inducible Tet-Off system, we demonstrated that deletion of the nucleotide resulted in a >2-fold decrease in the half-life of TAP-1 mRNA. However, the decrease of the half-life of TAP-1 mRNA is not mediated by nonsense-mediated mRNA decay because deletions of two additional nucleotides in the region, which corrected the nonsense mutation, did not restore TAP-1 mRNA stability. To our knowledge, this is the first evidence that the degradation of mRNA of an antigen presentation gene is involved in HLA class I down-regulation in malignant cells.
doi:10.1074/jbc.m300954200 pmid:12582163 fatcat:vgddpwbf6rb27atvanp2afsvdi