| 2005 |
Crystal structure of the N-terminal domain of SMG7 reveals a 14-3-3-like domain. Residues equivalent to phosphoserine-binding residues in canonical 14-3-3 proteins are conserved in SMG7 and mediate binding to phosphorylated UPF1. Mutation of these residues impairs UPF1 binding to SMG7 in vitro and UPF1 recruitment to cytoplasmic mRNA decay foci in vivo, establishing SMG7 as a phospho-adaptor that targets mRNAs associated with phosphorylated UPF1 for degradation. |
X-ray crystallography, in vitro binding assay with phosphoserine mutants, in vivo localization (mRNA decay foci) |
Molecular cell |
High |
15721257
|
| 2003 |
Human SMG7 (hSmg5/7a) copurifies with UPF1, UPF2, UPF3X, SMG1, and the catalytic subunit of protein phosphatase 2A (PP2A), and functions in dephosphorylation of UPF1 but not UPF2, indicating that SMG7 targets PP2A to UPF1. SMG7 is predominantly cytoplasmic in HEK293T cells. |
Co-purification/Co-IP, dephosphorylation assay, subcellular fractionation/Western blot |
RNA (New York, N.Y.) |
Medium |
12554878
|
| 1999 |
C. elegans smg-7 is required for nonsense-mediated mRNA decay; null alleles of smg-7 confer temperature-sensitive stabilization of nonsense mutant mRNAs, establishing smg-7 as an essential NMD factor in vivo. |
Genetic screen, cloning, null allele analysis, mRNA stability assay |
Genetics |
Medium |
9927455
|
| 2013 |
Crystal structure of the C. elegans SMG5-SMG7 complex shows the two 14-3-3-like domains heterodimerize in an unusual perpendicular back-to-back orientation. Structure-based mutants confirm the heterodimer interface is conserved and essential for efficient NMD in human cells. Heterodimerization increases the affinity of the SMG5-SMG7 complex for phosphorylated UPF1, and the degradative activity of the SMG5-SMG7 complex resides specifically in SMG7. |
X-ray crystallography, structure-based mutagenesis, NMD functional assay in human cells, binding affinity measurements |
Genes & development |
High |
23348841
|
| 2014 |
In vitro reconstitution with purified components shows that a short C-terminal segment of phosphorylated UPF1 containing the last two Ser-Gln motifs is recognized by the SMG5-SMG7 heterodimer of 14-3-3-like proteins. SMG5 and SMG7 form a heterodimer, whereas the SMG6 14-3-3-like domain is monomeric. The dominant SMG6-UPF1 interaction is phosphorylation-independent, establishing that SMG5-SMG7 and SMG6 have distinct, non-overlapping modes of UPF1 recognition. |
In vitro reconstitution with purified components, crystal structure of SMG6 14-3-3-like domain, binding assays |
Nucleic acids research |
High |
25013172
|
| 2016 |
SMG6 and SMG7 act on essentially the same endogenous NMD target transcripts, indicating extensive redundancy between the endonucleolytic (SMG6) and exonucleolytic (SMG7) decay routes. NMD target features include introns in 3' UTRs, upstream ORFs, and long 3' UTRs. |
Transcriptome profiling of knockdowns and rescues of UPF1, SMG6, and SMG7; meta-analysis |
RNA (New York, N.Y.) |
Medium |
27864472
|
| 2016 |
SMG7 is a novel p53-binding protein that promotes DNA damage-induced p53 stabilization. SMG7 knockout abrogates DNA damage-induced p53 stabilization and impairs p53-mediated p21 activation and cell cycle arrest. SMG7 physically interacts with Mdm2 and promotes ATM-mediated inhibitory phosphorylation of Mdm2 following ionizing radiation, thereby preventing Mdm2-mediated p53 degradation. |
Somatic gene knockout, Co-IP (SMG7-p53 and SMG7-Mdm2), Mdm2 phosphorylation assay, cell cycle analysis |
Cell discovery |
Medium |
27462439
|
| 2021 |
Loss of the SMG5-SMG7 pathway also inactivates the SMG6 endonucleolytic branch, demonstrating an unexpected functional dependency. Either SMG5 or SMG7 alone is sufficient to support SMG6-mediated endonucleolysis of NMD targets, establishing a two-factor authentication model where UPF1 phosphorylation and SMG5-SMG7 recruitment are both required to access SMG6 activity. |
siRNA depletion of SMG5 and SMG7, transcriptome-wide analysis, functional NMD assays |
Nature communications |
Medium |
34172724
|
| 2012 |
SMG7 interacts with SMG5 but not with PNRC2; PNRC2 preferentially complexes with SMG5. Tethering experiments show that SMG6 is required for UPF1-mediated efficient mRNA degradation. SMG5/SMG7-dependent NMD substrates show less overlap with PNRC2-dependent NMD substrates, suggesting partial segregation of NMD pathways. |
Co-IP, microarray analysis, tethering assay |
Nucleic acids research |
Medium |
23234702
|
| 2018 |
SMG7 interacts with SMG5 (confirmed by Co-IP), and this SMG5-SMG7 complex is functionally required for NMD. In contrast, no physical or functional interaction between SMG5 and PNRC2 was detected. UPF1 interacts with PNRC2 and triggers 5'-3' exonucleolytic decay in tethering assays; PNRC2 knockdown does not affect NMD reporter RNA levels, indicating PNRC2 is not required for NMD. |
Co-IP, tethering assay, siRNA knockdown, NMD reporter assay |
RNA (New York, N.Y.) |
Medium |
29348139
|
| 2007 |
Yeast Ebs1p, identified as the putative S. cerevisiae ortholog of human SMG7, physically interacts with the NMD helicase Upf1p. Overexpressed Ebs1p recruits Upf1p into cytoplasmic P-bodies, and Ebs1p itself localizes to P-bodies upon glucose starvation. Both loss and overexpression of Ebs1p stabilize NMD targets. |
Sequence alignment, Co-IP, fluorescence microscopy (P-body localization), mRNA stability assay |
Nucleic acids research |
Medium |
17984081
|
| 2019 |
SMG7 interacts with the CCR4-NOT deadenylase complex, and loss of the SMG7-deadenylase complex interaction increases the levels of transcripts regulated by UPF1-SMG7. In combination with Ago2 and UPF1, SMG7 mediates miRNA-targeted mRNA degradation in a 3'UTR-length-dependent manner. |
Co-IP (Ago2-UPF1-SMG7), siRNA knockdown, RNA-seq, reporter assay |
Nature communications |
Medium |
31519907
|
| 2019 |
DNA damage-induced SMG7-p53 binding requires phosphorylated Ser15 on p53. Substitution of conserved lysine K66 in the SMG7 14-3-3-like domain with glutamic acid (K66E) abolishes interactions with p53 and UPF1 in vitro. Unexpectedly, cells expressing SMG7 K66E retain p53 stabilization/activation and fully functional NMD, indicating that phosphoserine-dependent SMG7 binding is not the sole or essential mechanism for these functions. |
Knockin mutagenesis (K66E), co-IP, cell cycle and apoptosis assays, NMD reporter assay |
Scientific reports |
Medium |
31511540
|
| 2021 |
SMG7 is required for ATR-CHK1 axis activation upon genotoxic stress. SMG7-null cells exhibit attenuated phosphorylation of CHK1 and RPA32 and unhindered DNA replication after damage. Through its 14-3-3 domain, SMG7 directly interacts with Ser635-phosphorylated RAD17 and promotes chromatin retention of the 9-1-1 complex by RAD17-RFC, an essential step for CHK1 activation. SMG7 also controls G2-M transition and facilitates cell cycle recovery from replication stress. |
SMG7-null cells, Co-IP (SMG7-RAD17), chromatin fractionation, CHK1/RPA32 phosphorylation assay, DNA fiber assay |
Scientific reports |
Medium |
33820915
|
| 2024 |
Chemical cross-linking mass spectrometry (CLMS) identifies protein-protein interactions among SMG1, UPF2, and SMG7, revealing UPF2 as a bridging protein between SMG1 and SMG7. The UPF2 N-terminal region mediates most interactions with SMG7, while SMG7 interactions emerge predominantly from connecting loops rather than well-defined secondary structures. |
Chemical cross-linking mass spectrometry (CLMS), structural modelling |
International journal of molecular sciences |
Low |
38542156
|