An overlapped natural antisense lncRNA FCER1A-AS controls anaphylactic reaction by promoting FcεRIα expression

Abstract

Functioned as α-subunit of the high-affinity immunoglobulin E receptor (FcϵRIα), FcϵRIα plays a central role in the pathogenesis of Ig-E-mediated allergy and other IgE-related disorders. FcϵRIα is normally expressed only in limited spectrum of cells like basophils and mast cells, but the mechanism of controlling FcϵRIα expression in these cells is less well understood. In this study, we found fully overlapped natural antisense transcript (NATs) of FcϵRIα (FCER1A-AS) is co-expressed with cognate sense transcript (FCER1A-S) in IL-3 induced FcϵRIα-expressing cells or in high FcϵRIα-expressing cell line MC/9. When FCER1A-AS is selectively knocked down by CRISPR/RfxCas13d (CasRx) approach in MC/9, expression of mRNA and proteins of FCER1A-S is also markedly decreased. Furthermore, deficiency of FCER1A-AS along with lack of FCER1A-S expression is found in two different lines of gene-targeted mice in which FCER1A locus is disturbed at different sites. More importantly, the FCER1A-AS-deficient homozygous mice display similarly diminished anaphylactic reaction as FCER1A gene knockout mice. Thus, we uncovered in this investigation that the expression of FCER1A-S is positively regulated by co-expressed fully overlapped antisense transcript.