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First published online March 30, 2007
doi: 10.1242/10.1242/jcs.03429

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The role of GW/P-bodies in RNA processing and silencing

¹ Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA
² Department of Biochemistry and Molecular Biology, University of Calgary, 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

View larger version (54K): [in this window] [in a new window]   Fig. 1. GW bodies (GWBs) are heterogeneous structures with obvious differences in protein composition. (Top) HEp-2 cells stained with human anti-GWB serum (a prototype serum often used as a GWB marker and known to contain antibodies to GW182, hAgo2 and Ge-1, but not Dcp1; green) and rabbit anti-Dcp1 antibody (often used as a marker for P-bodies; red) demonstrate that not all GWBs contain Dcp1. (Bottom) HEp-2 cells stained with mouse anti-hAgo2 monoclonal (green) and rabbit anti-RCK/p54 (red) polyclonal antibodies demonstrate that not all foci containing RCK/p54 contain hAgo2. Conversely, not all foci that stain for hAgo2 contain RCK/p54. Arrows, GWBs that do not contain both protein factors. Arrowheads, GWBs that do contain both protein factors. Nuclei (blue) were counterstained with DAPI. Bar, 10 µm.

View larger version (75K): [in this window] [in a new window]   Fig. 2. A model linking RNAi and GW body (GWB) assembly and function. RNAi activity is triggered by siRNA/miRNA duplexes, which are first processed from either double-stranded RNA (dsRNA) or precursor microRNA (pre-miRNA), respectively, by the RNase-III-type endonuclease Dicer. These duplexes are then incorporated into RISC, where the passenger strand (black) is either cleaved and degraded or removed by the bypass mechanism (Matranga et al., 2005). This activation process and assembly of the guide strand (red) into RISC is thought to initiate early stages of GWB formation. Subsequent targeting by RISC results in further recruitment of one or more heteromeric protein complexes (which could include GW182 and RCK/p54) on the mRNA, which forms a specific RNP structure that causes post-transcriptional inhibition of gene expression (through siRNA-mediated cleavage or miRNA-mediated translational repression, depending on the degree of complementarity between the guide-strand RNA and its target mRNA). The targeted mRNA is eventually degraded by further recruitment of 5'-to-3' mRNA decay factors, which include the deadenylase Ccr4, decapping factors (LSm1-7 ring, Dcp complex) and the 5'-to-3' exonuclease Xrn1. The accumulation of RNA decay factors during degradation could be responsible for the size increases in GWBs, which makes them visible by conventional light microscopy. ORF, open reading frame.