Journal
NUCLEIC ACIDS RESEARCH
Volume 39, Issue 1, Pages 347-358Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq749
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Funding
- Spanish Ministry of Science and Innovation [SAF2008-00451, SAF2008-00479]
- 'Red Tematica de Investigacion Cooperativa en Cancer (RTICC)' from the 'Instituto de Salud Carlos III' [RD06/0020/1001, RD06/0020/0011]
- Autonomous Region of Madrid [CAM S-BIO-0214-2006]
- Human Frontiers Science Program [RGP39/2008]
- Consejeria de Educacion de la Comunidad de Madrid y Fondo Social Europeo
- Japan Society for the Promotion of Science
- Japan Science and Technology Corporation
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Yokohama Foundation for Advancement of Medical Science
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SMG-9 is part of a protein kinase complex, SMG1C, which consists of the SMG-1 kinase, SMG-8 and SMG-9. SMG1C mediated phosphorylation of Upf1 triggers nonsense-mediated mRNA decay (NMD), a eukaryotic surveillance pathway that detects and targets for degradation mRNAs harboring premature translation termination codons. Here, we have characterized SMG-9, showing that it comprises an N-terminal 180 residue intrinsically disordered region (IDR) followed by a well-folded C-terminal domain. Both domains are required for SMG-1 binding and the integrity of the SMG1C complex, whereas the C-terminus is sufficient to interact with SMG-8. In addition, we have found that SMG-9 assembles in vivo into SMG-9: SMG-9 and, most likely, SMG-8: SMG-9 complexes that are not constituents of SMG1C. SMG-9 self-association is driven by interactions between the C-terminal domains and surprisingly, some SMG-9 oligomers are completely devoid of SMG-1 and SMG-8. We propose that SMG-9 has biological functions beyond SMG1C, as part of distinct SMG-9-containing complexes. Some of these complexes may function as intermediates potentially regulating SMG1C assembly, tuning the activity of SMG-1 with the NMD machinery. The structural malleability of IDRs could facilitate the transit of SMG-9 through several macromolecular complexes.
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