Article
- The EMBO Journal (2006) 25, 5117 - 5125
- doi:10.1038/sj.emboj.7601377
Published online: 19 October 2006
Subject Categories:
Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex
Filip Glavan1, Isabelle Behm-Ansmant2, Elisa Izaurralde2 and Elena Conti1,3
- European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- Max-Planck-Institute for Developmental Biology, Tübingen, Germany
- Max-Planck-Institute of Biochemistry, Martinsried, Germany
Correspondence to:
Elena Conti, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, Heidelberg 69117, Germany. Tel.: +49 6221 387 536; Fax: +49 6221 387 306; E-mail: conti@embl-heidelberg.de or conti@embl.de
Received 26 May 2006; Accepted 7 September 2006
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.
Keywords:
- decay,
- EST1A,
- NMD,
- P-bodies,
- RNA degradation
