SMG6 (F6A1U) Rabbit mAb #35537

Nonsense-mediated decay (NMD) is a process by which prematurely terminated transcripts are degraded before they can be translated (1-3). There are two differential processes for NMD in higher eukaryotes, endonucleolytic and exonucleolytic, which are governed by SMG6 (also known as EST1A) or SMG5 and SMG7, respectively (1,4-8). SMG5-7 are structurally similar, but SMG6 contains a PIN domain with endonucleolytic activity. While SMG5 contains a similar domain, it lacks critical residues for endonuclease activity, and SMG7 does not contain a PIN domain (7). All three proteins are recruited to UPF1 when it becomes phosphorylated by SMG1, and from there, the NMD process significantly diverges. Upon binding to UPF1, SMG5 and SMG7 can recruit decaying and deadenylating protein complexes, resulting in subsequent mRNA degradation via the XRN1 exonuclease and the exosome (8,9). SMG6, however, promotes decay through cleaving nonspecific sites within 40 nucleotides of the premature termination codon (PTC) (7,10). Interestingly, SMG6-mediated decay depends on either a functional SMG5 or SMG7 (11). NMD pathways are species-specific, with Drosophila relying more on SMG6-mediated decay and yeast utilizing the decaying and deadenylating approach to mRNA turnover (12).