NKCLR3 impairs natural killer cell cytotoxicity by epigenetically targeting the Natural Cytotoxicity Triggering Receptor 1 (NCR1)

RNA-Seq reveals that NKCLR3 (NK cytotoxicity-associated long noncoding RNA 3, NONHSAT026854) is differentially expressed in VPA-treated human NK cells. To determine whether it is functionally important in NK cell cytotoxicity, we used a RNA reverse transcription-associated trap sequencing (RAT-Seq) approach to profile the genome-wide binding targets for NKCLR3. This dataset will help study the mechanisms underlying the role of NKCLR3 in NK cell cytotoxicity. Overall design: RAT-Seq was used to map the genome wide targets of lncRNAs. For RAT-Seq, NK-92MI cells were first cross-linked to fix the lncRNA-chromatin structure. The regulatory element-interacting RNAs were reverse transcribed in situ in the nucleus using lncRNA-specific complementary primers in a reaction mixture containing biotin-dCTP. The RNA-biotin cDNA chromatin complex was pulled down with streptavidin beads and the target gene DNAs were purified for library sequencing. Using RAT-Seq, we mapped the genome wide target for NKCLR3 (NK cytotoxicity-associated long noncoding RNA 3, NONHSAT026854). As the RAT control, RAT control dataset was generated by random oligo primers. NKCLR3 was negatively associated with the antitumor activity of NK cells. It was more highly expressed in VPA-treated NK cells.