The SMG5-SMG7 heterodimer directly recruits the CCR4-NOT deadenylase complex to mRNAs containing nonsense codons via interaction with POP2

被引:145
作者
Loh, Belinda [1 ]
Jonas, Stefanie [1 ]
Izaurralde, Elisa [1 ]
机构
[1] Max Planck Inst Dev Biol, Dept Biochem, D-72076 Tubingen, Germany
关键词
deadenylation; mRNA decay; NMD; UPF1; PREMATURE TRANSLATIONAL TERMINATION; HUMAN UPF1 HELICASE; MEDIATED DECAY; HUMAN-CELLS; ENDONUCLEOLYTIC CLEAVAGE; SURVEILLANCE COMPLEX; DECAPPING COMPLEX; MAMMALIAN-CELLS; 3' UTRS; YEAST;
D O I
10.1101/gad.226951.113
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nonsense-mediated mRNA decay (NMD) is a eukaryotic quality control mechanism that detects aberrant mRNAs containing nonsense codons and induces their rapid degradation. This degradation is mediated by SMG6, an NMD-specific endonuclease, as well as the SMG5 and SMG7 proteins, which recruit general mRNA decay enzymes. However, it remains unknown which specific decay factors are recruited and whether this recruitment is direct. Here, we show that SMG7 binds directly to POP2, a catalytic subunit of the CCR4-NOT deadenylase complex, and elicits deadenylation-dependent decapping and 5'-to-3' decay of NMD targets. Accordingly, a catalytically inactive POP2 mutant partially suppresses NMD in human cells. The SMG7-POP2 interaction is critical for NMD in cells depleted of SMG6, indicating that SMG7 and SMG6 act redundantly to promote the degradation of NMD targets. We further show that UPF1 provides multiple binding sites for decapping factors. These data unveil a missing direct physical link between NMD and the general mRNA decay machinery and indicate that NMD employs diverse and partially redundant mechanisms to ensure robust degradation of aberrant mRNAs.
引用
收藏
页码:2125 / 2138
页数:14
相关论文
共 58 条
[1]   A faux 3′-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay [J].
Amrani, N ;
Ganesan, R ;
Kervestin, S ;
Mangus, DA ;
Ghosh, S ;
Jacobson, A .
NATURE, 2004, 432 (7013) :112-118
[2]   SMG-5, required for C-elegans nonsense-mediated mRNA decay, associates with SMG-2 and protein phosphatase 2A [J].
Anders, KR ;
Grimson, A ;
Anderson, P .
EMBO JOURNAL, 2003, 22 (03) :641-650
[3]   A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay [J].
Behm-Ansmant, Isabelle ;
Gatfield, David ;
Rehwinkel, Jan ;
Hilgers, Valerie ;
Izaurralde, Elisa .
EMBO JOURNAL, 2007, 26 (06) :1591-1601
[4]   Absence of Dbp2p alters both nonsense-mediated mRNA decay and rRNA processing [J].
Bond, AT ;
Mangus, DA ;
He, F ;
Jacobson, A .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (21) :7366-7379
[5]   GW182 Proteins Directly Recruit Cytoplasmic Deadenylase Complexes to miRNA Targets [J].
Braun, Joerg E. ;
Huntzinger, Eric ;
Fauser, Maria ;
Izaurralde, Elisa .
MOLECULAR CELL, 2011, 44 (01) :120-133
[6]   Computational modeling and experimental analysis of nonsense-mediated decay in yeast [J].
Cao, D ;
Parker, R .
CELL, 2003, 113 (04) :533-545
[7]   Rapid deadenylation triggered by a nonsense codon precedes decay of the RNA body in a mammalian cytoplasmic nonsense-mediated decay pathway [J].
Chen, CYA ;
Shyu, AB .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (14) :4805-4813
[8]   Structural and functional insights into the human Upf1 helicase core [J].
Cheng, Zhihong ;
Muhlrad, Denise ;
Lim, Meng Kiat ;
Parker, Roy ;
Song, Haiwei .
EMBO JOURNAL, 2007, 26 (01) :253-264
[9]   Characterization of human Smg5/7a:: A protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1 [J].
Chiu, SY ;
Serin, G ;
Ohara, O ;
Maquat, LE .
RNA, 2003, 9 (01) :77-87
[10]   SMG5-PNRC2 is functionally dominant compared with SMG5-SMG7 in mammalian nonsense-mediated mRNA decay [J].
Cho, Hana ;
Han, Sisu ;
Choe, Junho ;
Park, Seung Gu ;
Choi, Sun Shim ;
Kim, Yoon Ki .
NUCLEIC ACIDS RESEARCH, 2013, 41 (02) :1319-1328