Abstract 1148 GRAS1 non-coding RNA protects against DNA damage and cell death

Non-coding RNA (ncRNA) gene products are involved in diverse biological processes including splicing, epigenetic regulation, gene expression, proliferation, and metabolism. The biological mechanisms by which ncRNAs may act to regulate cell survival remain poorly understood. We found that a non-coding RNA transcript, the Growth Regulator Antisense 1 RNA (GRAS1), is a positive regulator of cell growth. Expression of GRAS1 protects lung, colon, and neuronal cells from DNA damage, and loss of GRAS1 triggers cell death. Decreased levels of GRAS1 long non-coding RNA (lncRNA) resulted in upregulated expression of genes associated with DNA damage response, cell cycle progression, and p53 signaling pathways. Extensive DNA damage occurred within 24 hours of GRAS1 knockdown, with a significant increase in the number of γH2AX foci, indicating multiple double strand breaks per cell. We investigated the function of the GRAS1 gene further since this locus includes four different RNA isoforms. We tested the effects of GRAS1 perturbation on cell growth by cloning isoforms of the GRAS1 gene and evaluating the effects of their expression in complementing cell death and DNA damage in GRAS1 knockdown cells.