Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex.
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.
Cho
Hana
H
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Kim
Kyoung Mi
KM
Kim
Yoon Ki
YK
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D018389:Codon, Nonsense / Q000235:genetics; D022083:Cytoplasmic Structures / Q000378:metabolism; D015536:Down-Regulation; D004722:Endoribonucleases / Q000378:metabolism; D005914:Globins / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D012315:RNA Caps / Q000378:metabolism*; D020365:RNA Helicases; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
D018389:Codon, Nonsense; C437718:PNRC2 protein, human; D012315:RNA Caps; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D005914:Globins; D005979:Glutathione Peroxidase; D004722:Endoribonucleases; C466279:DCP1A protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human