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| Subject Categories: RNA | Structural Biology |
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| The EMBO Journal
(2006) 25, 5117–5125, doi:10.1038/sj.emboj.7601377 Published online 19 October 2006 |
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| Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex |
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| Filip Glavan1, Isabelle Behm-Ansmant2, Elisa Izaurralde2 and Elena Conti1, 3 |
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1 European Molecular Biology Laboratory (EMBL), Heidelberg, Germany 2 Max-Planck-Institute for Developmental Biology, Tübingen, Germany 3 Max-Planck-Institute of Biochemistry, Martinsried, Germany To whom correspondence should be addressed 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; Published online 19 October 2006. |
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| Abstract |
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| 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. |
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| Keywords: decay, EST1A, NMD, P-bodies, RNA degradation |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSRNA stability: is it the endo' the world as we know it? Nature Structural & Molecular Biology News and Views (01 Jan 2009) RESEARCHSMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells Nature Structural & Molecular Biology Article (01 Jan 2009) A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay The EMBO Journal Article (21 Mar 2007) Inter-kingdom conservation of mechanism of nonsense-mediated mRNA decay The EMBO Journal Article (04 Jun 2008) |
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