期刊
EMBO JOURNAL
卷 31, 期 17, 页码 3596-3606出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2012.218
关键词
3 ' UTR; antigen presentation; HLA-A; MHC class I; mRNA decay; NK cells; ubiquitin E3 ligase
资金
- Medical Research Council
- Wellcome Trust
- MRC [G9800943, G0701279, G9202171] Funding Source: UKRI
- Medical Research Council [G9202171, G0701279, G9800943] Funding Source: researchfish
RNA-binding E3 ubiquitin ligases were recently identified, though their function remains unclear. While studying the regulation of the MHC class I (MHC-I) pathway, we here characterize a novel role for ubiquitin in mRNA degradation. MHC-I molecules provide ligands for both cytotoxic T-lymphocytes as well as natural killer (NK) cells, and play a central role in innate and adaptive immunity. MHC-I cell-surface expression is closely monitored by NK cells, whose killer immunoglobulin-like receptors encode MHC-I-specific activatory and inhibitory receptors, implying that MHC-I expression needs to be tightly regulated. In a functional siRNA ubiquitome screen we identified MEX-3C, a novel RNA-binding ubiquitin E3 ligase, as responsible for the post-transcriptional, allotype-specific regulation of MHC-I. MEX-3C binds the 3'UTR of HLA-A2 mRNA, inducing its RING-dependent degradation. The RING domain of MEX-3C is not required for HLA-A2 cell-surface downregulation, but regulates the degradation of HLA-A2 mRNA. We have therefore uncovered a novel post-transcriptional pathway for regulation of HLA-A allotypes and provide a link between ubiquitination and mRNA degradation. The EMBO Journal (2012) 31, 3596-3606. doi: 10.1038/emboj.2012.218; Published online 3 August 2012 Subject Categories: RNA; proteins
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