We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex.
- Authors
Glavan, Filip; Behm-Ansmant, Isabelle; Izaurralde, Elisa; Conti, Elena
- Abstract
SMG6 and SMG5 are essential factors in nonsense-mediated mRNA decay, a conserved pathway that degrades mRNAs with premature translation termination codons. Both SMG5 and SMG6 have been predicted to contain a C-terminal PIN (PilT N-terminus) domain, present in proteins with ribonuclease activity. We have determined the structures of human SMG5 and SMG6 PIN domains. Although they share a similar overall fold related to ribonucleases of the RNase H family, they have local differences at the putative active site. SMG6 has the canonical triad of acidic residues that are crucial in RNase H for nuclease activity, while SMG5 lacks key catalytic residues. The structural differences are reflected at the functional level. Only the PIN domain of SMG6 has degradation activity on single-stranded RNA in vitro. This difference in catalytic activity is conserved in Drosophila, where an SMG6 with an inactive PIN domain inhibits NMD in a dominant-negative manner. Our findings suggest that the NMD machinery has intrinsic nuclease activity that is likely to contribute to the rapid decay of mRNAs that terminate translation prematurely.
- Publication
The EMBO journal, 2006, Vol 25, Issue 21, p5117
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7601377