Molecule of the Month
May 2010
SMG6 PIN Domain is an Endonuclease that Cleaves Nonsense mRNAs

Nonsense-mediated mRNA decay (NMD) is a translation-dependent mechanism to recognize and degrade mRNAs with termination codons in a molecular environment unfavorable for efficient translation termination. Among the previously identified trans-acting factors involved in NMD, the group of Oliver Mühlemann, in collaboration with Søren Lykke-Andersen and Torben Heick Jensen (Aarhus University, Denmark) identified human SMG6 as the endonuclease that cleaves nonsense mRNAs near the termination codon in the process of NMD (A; Eberle et al., 2009).
The endonucleolytic activity of SMG6 resides in its PIN domain, which forms an RNase H-like catalytic center (B; Glavan et al., 2006). The three aspartic acid residues highlighted in orange form the catalytic center of the endonuclease.

This work was carried out in the group of Prof. Oliver Mühlemann.


  • Andrea Eberle, Søren Lykke-Andersen, Oliver Mühlemann and Torben Heick Jensen;
    "SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells"
    Nat. Struct. Mol. Biol., 16, 49-55, (2009); doi:10.1038/nsmb.1530.
  • Filip Glavan, Isabelle Behm-Ansmant, Elisa Izaurralde and Elena Conti;
    "Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex"
    EMBO J., 25, 5117-5125, (2006); doi:10.1038/sj.emboj.7601377.