SIRT7 is an RNA-activated protein lysine deacylase [RIP-seq ribo-zero]

We report that RNA can increase the catalytic efficiency of SIRT7 and that SIRT7 can remove long chain fatty acyl groups more efficiently than removing acetyl groups. Truncation and mutagenesis studies revealed residues at both the amino and carboxyl termini of SIRT7 that are involved in RNA-binding and important for activity. RNA immunoprecipitation-sequencing (RIP-seq) identified ribosomal RNA (rRNA) as the predominant RNA binding partners of SIRT7. The associated RNA was able to effectively activate the deacetylase and defatty-acylase activities of SIRT7. These findings provide important insights into the biological functions of SIRT7, as well as an improved platform to develop SIRT7 modulators. Overall design: SIRT7 with a Flag tag was expressed in HEK293T cells. Anti-Flag antibody (Sigma #A2220) was used to pull down SIRT7 along with the RNA that were bound to SIRT7. The RNA associated with SIRT7 was examined using next-generation sequencing.