Proximity RNA labeling reveals functions of lncRNA in DNA damage response

Long non-coding RNAs (lncRNA) are emerging as important players to keep genome stability and associate with human diseases including cancers (Statello et al., Statello et al., Nature Reviews Molecular Cell Biology 22:96–118, 2021). However, the underlying mechanisms that lncRNAs contribute to DNA damage response are not fully known. One of the limitations is that current studies depend on the physical interaction between lncRNA and the decoy, so that weak interactions might not be detected. Here we applied a method to label proximal lncRNAs of gH2ax, a marker of DNA damage, by antibody-mediated protein A-ascorbate peroxidase 2 (APEX2) and discovered that several lncRNA co-localized within DNA damage sites, including BGL3 which binds BARD1 and SNHG12 which interacts with DNA-PK (Haemmig et al., Haemmig et al., Sci Transl Med, 2020; Hu et al., Hu et al., EMBO Journal 39:e104133, 2020). In addition, we proved that knockdown of SNHG12 sensitized human cervical cancer HeLa and colon cancer HCT116 cells to irradiation. Overall, our study provides a new method to explore the function of lncRNA in DNA damage response.