Tristetraprolin/ZFP36 regulates the turnover of autoimmune-associated HLA-DQ mRNAs

• DOI: 10.1101/337907
• Publication Date: 2018-06-06T19:30:01Z
• Authors: Laura Pisapia; Russell S. Hamilton; Federica Farina; Vito D’Agostino; Pasquale Barba; Maria Strazzullo; Alessandro Proven...; Carmen Gianfrani; Giovanna Del Pozzo
• Keywords: Tristetraprolin

Abstract We have previously demonstrated that the expression of HLA class II genes is regulated by binding a ribonucleoprotein complex affects mRNA processing. identified protein components transcripts encoding HLA-DR molecule. Here we investigate whether same RNA proteins interact with 3’UTR mRNAs HLA-DQ isotype. Specifically, focused on HLA-DQ2.5 molecule, expressed surface antigen presenting cells, and representing main susceptibility factor for celiac disease (CD). This encoded HLA-DQA1*05 HLA-DQB1*02 alleles, presents antigenic gluten peptides to CD4 + T lymphocytes, activating autoimmune response. Here, an additional component RNP complex, Tristetraprolin (TTP) or ZFP36, zinc-finger protein, widely described as modulating stability. TTP shows high affinity CD-associated in contrast lower HLA-DQA1*01 HLA-DQB1*05 non-CD associated alleles. Our silico analysis, confirmed molecular experiments, demonstrates specifically modulates stability disease.