Nonsense-mediated mRNA decay factor SMG5 (SMG5)

Nonsense-mediated mRNA decay factor SMG5 (SMG5) is an RNA-binding protein and essential effector in the nonsense-mediated mRNA decay (NMD) pathway, which eliminates mRNAs containing premature translation termination codons and maintains mRNA quality control[1][3][4][5]. SMG5 forms a heterodimer with SMG7 via conserved 14-3-3-like domains, enabling recruitment to phosphorylated UPF1, the central NMD regulator[5]. Its function is to mediate and promote the dephosphorylation of UPF1, facilitate degradation of NMD target mRNAs—predominantly through exonucleolytic pathways—and ensure faithful gene expression surveillance[3][4][1]. While it harbors a PIN domain structurally similar to RNases, SMG5 itself lacks nuclease activity but is vital for pathway execution via its protein interactions. Loss of SMG5 function can cause severe defects in NMD, dysregulation of cellular transcriptome, impaired spermatogenesis, and cell death through hyperactivation of stress pathways such as p38 MAPK[2][3]. SMG5 is not a direct target for therapeutic intervention, but dysregulation of NMD and related factors has emerging links to cancer and genetic disease[1][2].

Other names

EST1BKIAA1089hSMG-5LPTS-RP1LPTSRP1RP11-54H19.7SMG-5EST1-like protein BLPTS-interacting proteinSMG-5 homologEST1 telomerase component homolog BEst1p-like protein Bever shorter telomeres 1Bsmg-5 homolog

no therapeutic drugs target SMG5; it acts as a regulator in the NMD pathway