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RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA
Kedde, M., Strasser, M.J., Boldajipour, B., Oude Vrielink, J.A., Slanchev, K., le Sage, C., Nagel, R., Voorhoeve, P.M., van Duijse, J., Andersson Ørom, U., Lund, A.H., Perrakis, A., Raz, E., and Agami, R.
Kedde, M., Strasser, M.J., Boldajipour, B., Oude Vrielink, J.A., Slanchev, K., le Sage, C., Nagel, R., Voorhoeve, P.M., van Duijse, J., Andersson Ørom, U., Lund, A.H., Perrakis, A., Raz, E., and Agami, R. (2007) RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA. Cell. 131(7):1273-1286.
MicroRNAs (miRNAs) are inhibitors of gene expression capable of controlling processes in normal development and cancer. In mammals, miRNAs use a seed sequence of 6-8 nucleotides (nt) to associate with 3' untranslated regions (3'UTRs) of mRNAs and inhibit their expression. Intriguingly, occasionally not only the miRNA-targeting site but also sequences in its vicinity are highly conserved throughout evolution. We therefore hypothesized that conserved regions in mRNAs may serve as docking platforms for modulators of miRNA activity. Here we demonstrate that the expression of dead end 1 (Dnd1), an evolutionary conserved RNA-binding protein (RBP), counteracts the function of several miRNAs in human cells and in primordial germ cells of zebrafish by binding mRNAs and prohibiting miRNAs from associating with their target sites. These effects of Dnd1 are mediated through uridine-rich regions present in the miRNA-targeted mRNAs. Thus, our data unravel a novel role of Dnd1 in protecting certain mRNAs from miRNA-mediated repression.