UC San Diego

Psoriasis is a skin condition characterized by skin thickening, inflammation, and dysfunction in the epidermal skin barrier. At the molecular level, psoriasis occurs as keratinocytes experience impaired differentiation and excessive proliferation. Long non-coding RNAs (lncRNAs) are found within the non-coding region of the genome, and while they are known to be more cell and tissue-specific than other RNAs, their role in diseases is not yet fully understood. Using a CRISPR interference (CRISPRi) screen and genome-wide association study (GWAS), lncRNAs involved in keratinocyte proliferation were mapped to psoriasis loci, and our laboratory identified Filaggrin antisense RNA 1 (FLG-AS1) as a top candidate. The single nucleotide polymorphism (SNP) within FLG-AS1, rs12130219 (A>G), is associated with an increase the risk of psoriasis, but the specific mechanism is still unclear. It was first determined through an enhancer reporter assay that this SNP does not act through transactivation. Experiments perturbing expression of FLG-AS1 RNA found that FLG-AS1 promotes keratinocyte proliferation in both cell culture and organotypic skin culture. We proposed that rs12130219 may be linked to psoriasis through its effect on FLG-AS1 RNA expression.