Suppressor with morphogenetic effect on genitalia protein 7 (SMG7)

Suppressor with morphogenetic effect on genitalia protein 7 (SMG7) is a crucial adapter protein in the nonsense-mediated mRNA decay (NMD) pathway, a cellular surveillance mechanism that degrades mRNAs containing premature termination codons (UniProt: Q92540). SMG7 functions by recognizing phosphorylated UPF1 through its N-terminal 14-3-3-like domain and subsequently recruiting the CCR4-NOT deadenylase complex via its C-terminal domain to initiate mRNA degradation (Jonas et al., 2013, Genes & Dev). Beyond its role in NMD, SMG7 is involved in telomere maintenance and the regulation of various physiological transcripts (NCBI Gene: 23511). In therapeutic contexts, SMG7 is a target of interest for cancer treatment, as inhibiting NMD can stabilize transcripts with nonsense mutations, leading to the production of neoantigens that enhance immune responses (Loh et al., 2013, Genes & Dev). It is also being explored for genetic diseases caused by nonsense mutations, where NMD suppression could allow for the expression of partially functional proteins (PubMed: 23932589). While no SMG7-specific drugs are currently FDA-approved, research into small-molecule inhibitors and antisense therapies is ongoing to modulate mRNA stability for therapeutic benefit (Baird et al., 2018, Bioessays). Potential safety concerns include the risk of global NMD disruption and the resulting accumulation of potentially toxic truncated proteins.

Other names

SMG-7EST1CEST1-like protein CProtein SMG7

Inhibition of nonsense-mediated mRNA decay by preventing the recruitment of the CCR4-NOT deadenylase complex to phosphorylated UPF1.