The noncoding RNA GRAS1 interacts with NKAP and protects against DNA damage and cell death

Noncoding RNA (ncRNA) gene products may be involved in diverse biological processes. We find that the growth regulator antisense 1 (GRAS1) noncoding RNA (ncRNA) transcript protects against cell death in human cell lines. GRAS1 ncRNA is one of the biomolecules produced from the EPB41L4A- AS1 gene locus, which also encodes the SNORA13 snoRNA and the TIGA1 protein. Specific knockdown of GRAS1 ncRNA leads to cell death and extensive DNA damage. We used RNA antisense purification and mass spectrometry to identify NF-κB activating protein (NKAP) as a direct interaction partner of GRAS1 ncRNA. NKAP was degraded in a proteasome-dependent manner after GRAS1 knockdown. Complementation with overexpressed NKAP mitigated the DNA damage effects of GRAS1 knockdown and confirmed the contribution of both NKAP and GRAS1 to cell growth. In summary, we find that GRAS1 and NKAP directly interact and protect against DNA damage and cell death in lung cancer and colon cancer cell lines. Our identification of a functional GRAS1 transcript reveals new information about the biomolecules produced by the EPB41L4A- AS1 locus and their contributions to human cell growth.