Human IL12RB1 expression is allele-biased and produces a novel IL12 response regulator. Genes Immun 2019 Mar;20(3):181-197
Date
03/31/2018Pubmed ID
29599514Pubmed Central ID
PMC6165718DOI
10.1038/s41435-018-0023-2Scopus ID
2-s2.0-85044534384 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
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 (IL12Rβ1, 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.
Author List
Reeme AE, Claeys TA, Aggarwal P, Turner AJ, Routes JM, Broeckel U, Robinson RTAuthors
Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of WisconsinAllison Reeme in the CTSI department at Medical College of Wisconsin - CTSI
Amy Turner Research Scientist I in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AllelesCells, Cultured
Heterogeneous-Nuclear Ribonucleoprotein Group F-H
Humans
Interleukin-12
Jurkat Cells
Lung
Protein Binding
Protein Isoforms
RNA Splicing
Receptors, Interleukin-12
T-Lymphocytes
