{"doi":"10.3389/fimmu.2019.03034","title":"Tuning of NK-Specific HLA-C Expression by Alternative mRNA Splicing","abstract":"A complex system regulating HLA-C expression in NK cells, driven by an NK-specific promoter that produces alternatively spliced variants of the 5 -UTR has been recently identified. Exon content of the NK-specific 5 -UTR varies strikingly across HLA-C alleles, with some exons being allele specific. In order to investigate the possibility that allelic variation in the 5 -UTR modulates HLA-C expression levels, cDNAs containing several distinct classes of 5 -UTR were compared. Subtle changes in 5 -UTR content had a significant effect on the expression of HLA-C * 03 and HLA-C * 12 cDNA clones, suggesting that alternative splicing can fine-tune the level of protein expression. The HLA-C * 06 allele was found to be highly expressed in relation to the other alleles studied. However, its increased expression was primarily associated with differences in the peptide-binding groove. Although the impact of allele-specific alternative splicing of NK-Pro transcripts on protein levels can be modest when compared with the effect of changes in peptide-loading, alternative splicing may represent an additional regulatory mechanism to fine-tune HLA-C levels within NK cells in distinct tissue environments or at different stages of maturation in order to achieve optimal levels of missing-self recognition.","journal":"Frontiers in Immunology","year":2020,"id":87957,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":447994,"name":"Brian Rothbard","orcid":null,"position":1,"is_corresponding":false},{"id":446757,"name":"Amy Zhang","orcid":"0000-0002-6536-3609","position":2,"is_corresponding":false},{"id":352048,"name":"Paul W. Wright","orcid":null,"position":3,"is_corresponding":false},{"id":423546,"name":"Hongchuan Li","orcid":"0000-0002-3501-4299","position":4,"is_corresponding":false},{"id":446758,"name":"Victoria E. Walker-Sperling","orcid":"0000-0001-7847-7931","position":5,"is_corresponding":false},{"id":37727,"name":"Mary Carrington","orcid":"0000-0002-2692-2180","position":6,"is_corresponding":false},{"id":262407,"name":"Stephen K. Anderson","orcid":"0000-0002-7856-4266","position":7,"is_corresponding":false},{"id":396078,"name":"Frederick J. Goodson-Gregg","orcid":null,"position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:00:56.736935Z","pmid":"31998314","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}