title: SMG5-PNRC2 is functionally dominant compared with SMG5-SMG7 in mammalian nonsense-mediated mRNA decay.
abstract: In mammals, nonsense-mediated mRNA decay (NMD) functions in post-transcriptional gene regulation as well as mRNA surveillance. A key NMD factor, Upf1, becomes hyperphosphorylated by SMG1 kinase during the recognition of NMD substrates. Hyperphosphorylated Upf1 interacts with several factors including SMG5, SMG6, SMG7 and PNRC2 to trigger rapid mRNA degradation. However, the possible cross-talk among these factors and their selective use during NMD remain unknown. Here, we show that PNRC2 is preferentially complexed with SMG5, but not with SMG6 or SMG7, and that downregulation of PNRC2 abolishes the interaction between SMG5 and Dcp1a, a component of the decapping complex. In addition, tethering experiments reveal the function of Upf1, SMG5 and PNRC2 at the same step of NMD and the requirement of SMG6 for Upf1 for efficient mRNA degradation. Intriguingly, microarray results reveal the significant overlap of SMG5-dependent NMD substrates more with PNRC2-dependent NMD substrates than with SMG7-dependent NMD substrates, suggesting the functional dominance of SMG5-PNRC2, rather than SMG5-SMG7, under normal conditions. The results provide evidence that, to some extent, endogenous NMD substrates have their own binding preference for Upf1-interacting adaptors or effectors.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.forename: Sisu
authors.initials: S
authors.lastname: Han
authors.forename: Junho
authors.initials: J
authors.lastname: Choe
authors.forename: Seung Gu
authors.initials: SG
authors.lastname: Park
authors.forename: Sun Shim
authors.initials: SS
authors.lastname: Choi
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D059365:Nonsense Mediated mRNA Decay; D020365:RNA Helicases; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D004722:Endoribonucleases
chemical_list: D002352:Carrier Proteins; D020365:RNA Helicases; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D019098:Telomerase; D015534:Trans-Activators; C437718:PNRC2 protein, human; C515801:SMG5 protein, human; C494578:SMG7 protein, human; C512261:SMG6 protein, human; D004722:Endoribonucleases; C101828:UPF1 protein, human