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First published online December 3, 2008
doi: 10.1242/10.1242/jcs.036905
Research Article |
1 Departments of Oral Biology and Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA
2 Department of Biochemistry and Molecular Biology, University of Calgary, Alberta T2N 4N1, Canada
3 Division of Rheumatology and Clinical Immunology, Department of Medicine and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA
Author for correspondence (e-mail: echan{at}ufl.edu)
Accepted 29 August 2008
RNA interference is triggered by small interfering RNA and microRNA, and is a potent mechanism in post-transcriptional regulation for gene expression. GW182 (also known as TNRC6A), an 182-kDa protein encoded by TNRC6A, is important for this process, although details of its function remain unclear. Here, we report a novel 210-kDa isoform of human GW182, provisionally named trinucleotide GW1 (TNGW1) because it contains trinucleotide repeats in its mRNA sequence. TNGW1 was expressed independently of GW182 and was present in human testis and various human cancer cells. Using polyclonal and monoclonal antibodies, we detected TNGW1 in only 
30% of GW bodies. Expression of EGFP-tagged TNGW1 in HeLa cells was colocalized to cytoplasmic foci enriched in Ago2 (also known as EIF2C2) and RNA decay factors. Tethering TNGW1 or GW182 to the 3'-UTR of a luciferase-reporter mRNA led to strong repression activity independent of Ago2, whereas the tethered Ago2-mediated suppression was completely dependent on TNGW1 and/or GW182. Our data demonstrated that GW182 and, probably, TNGW1 acted as a repressor in Ago2-mediated translational silencing. Furthermore, TNGW1 might contribute to diversity in the formation and function of GW and/or P bodies.
Key words: GW182 (TNRC6A), Argonaute 2 (EIF2C2), Translational repression, GW body, P body, Trinucleotide repeat
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 S. Li, S. L. Lian, J. J. Moser, M. L. Fritzler, M. J. Fritzler, M. Satoh, and E. K. L. Chan Identification of GW182 and its novel isoform TNGW1 as translational repressors in Ago2-mediated silencing Development, January 1, 2009; 136(1): e1 - e1. [Full Text]
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