Regulation of poly(a)-specific ribonuclease activity by reversible lysine acetylation.
Poly(A)-specific ribonuclease (PARN) is a 3'-exoribonuclease that plays an important role in regulating the stability and maturation of RNAs. Recently, PARN has been found to regulate the maturation of the human telomerase RNA component (hTR), a noncoding RNA required for telomere elongation. Specifically, PARN cleaves the 3'-end of immature, polyadenylated hTR to form the mature, nonpolyadenylated template. Despite PARN's critical role in mediating telomere maintenance, little is known about how PARN's function is regulated by post-translational modifications. In this study, using shRNA- and CRISPR/Cas9-mediated gene silencing and knockout approaches, along with 3'-exoribonuclease activity assays and additional biochemical methods, we examined whether PARN is post-translationally modified by acetylation and what effect acetylation has on PARN's activity. We found PARN is primarily acetylated by the acetyltransferase p300 at Lys-566 and deacetylated by sirtuin1 (SIRT1). We also revealed how acetylation of PARN can decrease its enzymatic activity both in vitro, using a synthetic RNA probe, and in vivo, by quantifying endogenous levels of adenylated hTR. Furthermore, we also found that SIRT1 can regulate levels of adenylated hTR through PARN. The findings of our study uncover a mechanism by which PARN acetylation and deacetylation regulate its enzymatic activity as well as levels of mature hTR. Thus, PARN's acetylation status may play a role in regulating telomere length.
['Dejene|Eden A|EA|0000-0002-2232-4220', 'Li|Yixuan|Y|', 'Showkatian|Zahra|Z|', 'Ling|Hongbo|H|', 'Seto|Edward|E|']
D000107:Acetylation D005095:Exoribonucleases D055786:Gene Knockout Techniques D045325:HCT116 Cells D006367:HeLa Cells D006801:Humans D008239:Lysine D056564:Sirtuin 1 D019098:Telomerase D016615:Telomere D059505:Telomere Homeostasis
acetylation poly(A)-specific ribonuclease (PARN) human telomerase RNA component (hTR) noncoding RNA polyadenylation p300 sirtuin1 (SIRT1) RNA processing genome maintenance post-translational modification (PTM) protein acetylation sirtuin 1 (SIRT1)