Serman A, Le Roy F, Aigueperse C, Kress M, Dautry F, Weil D
CNRS FRE2937, Institut André Lwoff, 7 rue Guy Moquet, 94801 Villejuif cedex, France.
Nucleic Acids Res. 2007;35(14):4715-27. doi: 10.1093/nar/gkm491. Epub 2007 Jun 29.
GW bodies (or P-bodies) are cytoplasmic granules containing proteins involved in both mRNA degradation and storage, including the RNA interference machinery. Their mechanism of assembly and function are still poorly known although their number depends upon the flux of mRNA to be stored or degraded. We show here that silencing of the translational regulator CPEB1 leads to their disappearance, as reported for other GW body components. Surprisingly, the same results were obtained with several siRNAs targeting genes encoding proteins unrelated to mRNA metabolism. The disappearance of GW bodies did not correlate with the silencing activity of the siRNA and did not inhibit further silencing by siRNA. Importantly, in most cases, GW bodies were rapidly reinduced by arsenite, indicating that their assembly was not prevented by the inhibition of the targeted or off-target genes. We therefore propose that some siRNA sequences affect mRNA metabolism so as to diminish the amount of mRNA directed to the GW bodies. As an exception, GW bodies were not reinduced following Rck/p54 depletion by interference, indicating that this component is truly required for the GW body assembly. Noteworthy, Rck/p54 was dispensable for the assembly of stress granules, in spite of their close relationship with the GW bodies.
GW小体（或P小体）是细胞质颗粒，含有参与mRNA降解和储存的蛋白质，包括RNA干扰机制。尽管它们的数量取决于要储存或降解的mRNA通量，但其组装和功能机制仍知之甚少。我们在此表明，翻译调节因子CPEB1的沉默会导致它们消失，这与其他GW小体成分的情况相同。令人惊讶的是，用几种靶向编码与mRNA代谢无关的蛋白质的基因的小干扰RNA（siRNA）也得到了相同的结果。GW小体的消失与siRNA的沉默活性无关，也不抑制siRNA的进一步沉默。重要的是，在大多数情况下，亚砷酸盐能迅速重新诱导GW小体的形成，这表明靶向基因或脱靶基因的抑制并未阻止其组装。因此，我们提出一些siRNA序列会影响mRNA代谢，从而减少进入GW小体的mRNA量。作为一个例外，干扰导致Rck/p54缺失后，GW小体不会重新形成，这表明该成分是GW小体组装真正需要的。值得注意的是，尽管应激颗粒与GW小体关系密切，但Rck/p54对于应激颗粒的组装是可有可无的。
