Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

The introduction of RNA-DNA differences underlies interindividual variation in the human IL12RB1 mRNA repertoire. Proc Natl Acad Sci U S A 2015 Dec 15;112(50):15414-9

Date

12/02/2015

Pubmed ID

26621740

Pubmed Central ID

PMC4687591

DOI

10.1073/pnas.1515978112

Scopus ID

2-s2.0-84950107978   6 Citations

Abstract

Human interleukin 12 and interleukin 23 (IL12/23) influence susceptibility or resistance to multiple diseases. However, the reasons underlying individual differences in IL12/23 sensitivity remain poorly understood. Here we report that in human peripheral blood mononuclear cells (PBMCs) and inflamed lungs, the majority of interleukin-12 receptor I?1 (IL12RB1) mRNAs contain a number of RNA-DNA differences (RDDs) that concentrate in sequences essential to IL12RI?1's binding of IL12p40, the protein subunit common to both IL-12 and IL-23. IL12RB1 RDDs comprise multiple RDD types and are detectable by next-generation sequencing and classic Sanger sequencing. As a consequence of these RDDs, the resulting IL12RI?1 proteins have an altered amino acid sequence that could not be predicted on the basis of genomic DNA sequencing alone. Importantly, the introduction of RDDs into IL12RB1 mRNAs negatively regulates IL12RI?1's binding of IL12p40 and is sensitive to activation. Collectively, these results suggest that the introduction of RDDs into an individual's IL12RB1 mRNA repertoire is a novel determinant of IL12/23 sensitivity.

Author List

Turner AJ, Aggarwal P, Miller HE, Waukau J, Routes JM, Broeckel U, Robinson RT

Authors

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin
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

Adult
Base Sequence
DNA
Gene Expression Regulation
Humans
Interleukin-12
Lung
Models, Biological
Molecular Sequence Data
Phytohemagglutinins
Pneumonia
Protein Binding
RNA
RNA, Messenger
Receptors, Interleukin-12
Recombinant Proteins