The RNA binding protein Musashi1 regulates apoptosis, gene expression and stress granule formation in urothelial carcinoma cells.
Bottom Line: Up-regulated mRNAs contained a highly significantly greater number and density of Musashi binding sites.A significant number of up-regulated genes encoded components of stress granules (SGs), an organelle involved in translational regulation and mRNA turnover, and impacting on apoptosis.Accordingly, heat shock induced SG formation was augmented by Musashi1 down-regulation.
Affiliation: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.Show MeSH
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Mentions: Among the genes significantly up-regulated upon MSI1 knockdown, we noted several reported to influence RNA stability and turnover, such as CCNL1 , RRAS , APP1  and TIA-1 , which increased 2.1-, 3.1-, 2.9- and 3.1-fold, respectively, and in particular, some associated with SGs. Of 35 proteins listed as SG components in a recent review  encoded by genes represented on the microarray, 9 were significantly up-regulated following Musashi1 knockdown (Table 2). In addition, for five others, closely related genes or genes encoding subunits were up-regulated. Only four such genes would have been expected by chance. Quantitative RT-PCR confirmed up-regulation of RRAS (P-value = 0.0065) and APP1 (P-value = 0.039) after MSI1 siRNA treatment, whereas up-regulation of TIA-1 and CCNL1 was much weaker than expected from the microarray data (Fig. 6). We therefore evaluated the effect of MSI1 depletion on the formation of SGs, which were detected by a specific antibody against TIA-1. After MSI1 depletion, the number of 5637 cells forming several SGs after heat shock increased strongly and highly significantly compared to cells treated with IR-siRNA (Fig. 7). Intriguingly, 639v cells did not form SGs under either condition.
Affiliation: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.