LncRNA RP5-998N21.4 promotes immune defense through upregulation of IFIT2 and IFIT3 in schizophrenia

We recently identified a schizophrenia-associated upregulated long noncoding RNA (lncRNA) RP5-998N21.4 by transcriptomic analysis of monozygotic twins discordant for schizophrenia. Importantly, we found that genes coexpressed with RP5-998N21.4 were enriched in immune defense-related biological processes in twin subjects and in RP5-998N21.4-overexpressing (OE) SK-N-SH cell lines. We then identified two genes encoding interferon-induced protein with tetratricopeptide repeat (IFIT) 2 and 3, which play an important role in immune defense, as potential targets of RP5-998N21.4 by integrative analysis of RP5-998N21.4OE-induced differentially expressed genes (DEGs) in SK-N-SH cells and RP5-998N21.4-coexpressed schizophrenia-associated DEGs from twin subjects. We further demonstrated that RP5-998N21.4 positively regulates the transcription of IFIT2 and IFIT3 by binding to their promoter regions and affecting their histone modifications. In addition, as a general nuclear coactivator, RMB14 (encoding RNA binding motif protein 14) was identified to facilitate the regulatory role of RP5-998N21.4 in IFIT2 and IFIT3 transcription. Overall design: Total RNA were extracted from RP5-998N21.4 overexpressed (n=2) or wild type (WT, n=2) SK-N-SH cells and performed by deep sequencing, using Illumina.