Human Proline-Rich Nuclear Receptor Coregulatory Protein 2 Mediates an Interaction between mRNA Surveillance Machinery and Decapping Complex

• DOI: 10.1016/j.molcel.2008.11.022
• Publication Date: 2009-01-16T04:29:04Z
• Authors: Hana Cho; Kyoung Mi Kim; Yoon Ki Kim
• Keywords: RNA Caps; Glutathione Peroxidase; 0303 health sciences; RNA Stability; Down-Regulation; Receptors, Cytoplasmic and Nuclear; Cell Biology; Models, Biological; Globins; Protein Transport; 03 medical and health sciences; Codon, Nonsense; COS Cells; Chlorocebus aethiops; Endoribonucleases; Animals; Cytoplasmic Structures; Humans; RNA, Messenger; Phosphorylation; Molecular Biology; RNA Helicases; HeLa Cells; Protein Binding

Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism by which aberrant mRNAs harboring premature termination codons are degraded before translation. However, to date, how NMD machinery recruits the general decay complex to faulty mRNAs and degrades those mRNAs remains unclear. Here we identify human proline-rich nuclear receptor coregulatory protein 2 (PNRC2) as a Upf1- and Dcp1a-interacting protein. Downregulation of PNRC2 abrogates NMD, and artificially tethering PNRC2 downstream of a normal termination codon reduces mRNA abundance. Accordingly, PNRC2 preferentially interacts with hyperphosphorylated Upf1 compared with wild-type Upf1 and triggers movement of hyperphosphorylated Upf1 into processing bodies (P bodies). Our observations suggest that PNRC2 plays an essential role in mammalian NMD, mediating the interaction between the NMD machinery and the decapping complex, so as to target the aberrant mRNA-containing RNPs into P bodies.