title: The Minor MHC Class I Gene UDA of Ducks Is Regulated by Let-7 MicroRNA.
abstract: In many nonmammalian vertebrates, the genomic organization of the MHC class I region leads to biased expression of a single classical MHC class I gene coevolving with TAP transporters, whereas class I genes are poorly expressed. This contrasts to the three codominantly expressed classical MHC class I genes in humans and mice. In a sequenced haplotype from White Pekin duck, Anas platyrhynchos, there is one predominantly expressed MHC class I, UAA, although they have five MHC class I genes in the complex, arranged TAP1-TAP2-UAA-UBA-UCA-UDA-UEA The UAA gene, situated proximal to the TAP2 gene, is expressed at levels 10-fold greater than that of another expressed gene, UDA. Three duck MHC class I genes (UBA, UCA, and UEA) are predicted to be partially or completely inactivated by promoter defects, introduction of in-frame stop codon, or the lack of a polyadenylation signal. In this study, we confirm that UBA, UCA, and UEA are indeed inactivated through genetic defects at the promoter, whereas UAA and UDA have functionally equivalent promoters. To examine promoter accessibility, we performed bisulfite sequencing and show that none of the MHC class I promoters are inactivated by methylation. We determine that UDA is differentially regulated through its 3' untranslated region. Namely, expression of UDA is downregulated by let-7 microRNA, whereas the predominantly expressed MHC class I UAA is not. Regulation of UDA by let-7 microRNA suggests that the lower expression level is maintained for its function in immunity.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada; and.
authors.forename: Wing Fuk
authors.identifier: 0000-0002-8719-7787
authors.initials: WF
authors.lastname: Chan
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada; and.
authors.forename: Julie A
authors.identifier: 0000-0001-8091-8249
authors.initials: JA
authors.lastname: Parks-Dely
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada; and bmagor@ualberta.ca kmagor@ualberta.ca.
authors.forename: Brad G
authors.identifier: 0000-0003-4819-8530
authors.initials: BG
authors.lastname: Magor
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada; and Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta T6G 2E1, Canada bmagor@ualberta.ca kmagor@ualberta.ca.
authors.forename: Katharine E
authors.identifier: 0000-0002-9331-1486
authors.initials: KE
authors.lastname: Magor
mesh_terms: D000818:Animals; D004372:Ducks / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics*; D005805:Genes, MHC Class I / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D015395:Histocompatibility Antigens Class I; D035683:MicroRNAs