Post‐translational Modification of Poly (A)‐Specific Ribonuclease Regulates its Enzymatic Activity

Abstract

Post‐translational protein modifications (PTMs), such as acetylation, play an important role in mediating the function, expression, localization, and interactions of proteins. Protein acetylation is a reversible process that is tightly regulated by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Lysine acetylation of non‐histone proteins has been reported to affect their enzymatic activity, stability, and complex formation. However, the exact role of acetylation on non‐histone substrates is protein‐specific. Examination of a published dataset identifying acetylated lysine enriched substrates revealed that Poly (A)‐specific ribonuclease (PARN) may be post‐translationally modified by acetylation. PARN is a 3′ exoribonuclease; thus, its enzymatic activity allows it to cleave RNA bases at the 3′ end, one nucleotide at a time. PARN has the highest substrate affinity for adenosines; therefore it is also referred to as a deadenylase. Adenosine repeats (poly (A)) on the 3′ end of RNA prevent mature transcripts from degradation by nucleases, especially during transport from the nucleus to the cytoplasm for translation. Thus, removal of poly (A) tails by deadenylase enzymes such as PARN promotes mRNA decay. PARN's exoribonuclease activity plays an important role in many biological processes, such as embryogenesis, telomere maintenance, and DNA damage response. However, very little is known about how PARN is regulated in humans. The objective of this research is to investigate whether PARN is post‐translationally regulated by acetylation and whether this modification affects its biological function. Our findings revealed that PARN's activity is tightly regulated by acetylation in humans, and that acetylation plays a key role in mediating PARN's enzymatic activity.Support or Funding InformationThis research was supported by the National Cancer Institute of the National Institutes of Health under award number [3R01CA187040‐05S1]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.