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

Abstract

Functioned as -subunit of the high-affinity immunoglobulin E receptor (Fc{varepsilon} RI), Fc{varepsilon} RI plays a central role in the pathogenesis of Ig-E-mediated allergy and other IgE-related disorders. Fc{varepsilon} RI is normally expressed only in limited spectrum of cells like basophils and mast cells, but the mechanism of controlling Fc{varepsilon} RI expression in these cells is less well understood. In this study, we found fully overlapped natural antisense transcript (NATs) of Fc{varepsilon} RI (FCER1A-AS) is co-expressed with cognate sense transcript (FCER1A-S) in IL-3 induced Fc{varepsilon} RI-expressing cells or in high Fc{varepsilon} RI-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.