Nonsense mediated mRNA decay factor SMG6 (SMG6)

Nonsense mediated mRNA decay factor SMG6 (SMG6) is an evolutionarily conserved RNA endonuclease that plays a critical role in nonsense-mediated mRNA decay (NMD), a cellular quality-control pathway that degrades mRNAs containing premature termination codons, thereby preventing the production of truncated and potentially harmful proteins[2][4]. SMG6 contains a C-terminal PIN domain responsible for its catalytic activity, which uniquely enables it to cleave substrate mRNAs near the nonsense codon[2][3][6]. In addition to its function in mRNA surveillance, SMG6 is also a cofactor in the telomerase complex, participating in the maintenance of chromosome ends, although its role in telomere length homeostasis is secondary to its primary function in NMD[1][4]. SMG6 is essential for embryonic development and for the differentiation and identity switch of stem cells, but its complete absence is lethal at the blastocyst stage in mice[1]. Mutations or dysregulation of SMG6 are implicated in cancer and certain neurological disorders[4]. There are currently no known drugs that directly target SMG6, and loss of its function could be deleterious due to its fundamental roles in mRNA quality control and genome stability.

Other names

Telomerase-binding protein EST1AEST1AhEST1AKIAA0732C17orf31Smg-6 homologhSmg5/7aEver shorter telomeres 1AEST1 telomerase component homolog Atelomerase-binding protein EST1Anonsense mediated mRNA decay factortelomerase subunit EST1A

Endonucleolytic cleavage of premature stop codon-containing mRNAs leading to mRNA degradation, Regulation of gene expression via nonsense-mediated decay