Human IL12RB1 expression is allele-biased and produces a novel IL12 response regulator.
Genes Immun
; 20(3): 181-197, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-29599514
ABSTRACT
Human IL12RB1 is an autosomal gene that is essential for mycobacterial disease resistance and T cell differentiation. Using primary human tissue and PBMCs, we demonstrate that lung and T cell IL12RB1 expression is allele-biased, and the extent to which cells express one IL12RB1 allele is unaffected by activation. Furthermore following its expression the IL12RB1 pre-mRNA is processed into either IL12RB1 Isoform 1 (IL12Rß1, a positive regulator of IL12 responsiveness) or IL12RB1 Isoform 2 (a protein of heretofore unknown function). T cells choice to process pre-mRNA into Isoform 1 or Isoform 2 is controlled by intragenic competition of IL12RB1 exon 9-10 splicing with IL12RB1 exon 9b splicing, as well as an IL12RB1 exon 9b-associated polyadenylation site. Heterogeneous nuclear ribonucleoprotein H (hnRNP H) binds near the regulated polyadenylation site, but is not required for exon 9b polyadenylation. Finally, microRNA-mediated knockdown experiments demonstrated that IL12RB1 Isoform 2 promotes T cell IL12 responses. Collectively, our data support a model wherein tissue expression of human IL12RB1 is allele-biased and produces an hnRNP H-bound pre-mRNA, the processing of which generates a novel IL12 response regulator.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Empalme del ARN
/
Interleucina-12
/
Alelos
/
Receptores de Interleucina-12
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Genes Immun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
BIOLOGIA MOLECULAR
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos