Inhaltszusammenfassung

Axis formation of the Drosophila embryo is determined by the localized expression of specific mRNAs and proteins. This asymmetric distribution is already established during oogenesis in the mother. Oskar (Osk), which induces the formation of the posterior axis is among the first determinants to localize to the posterior pole of the egg-to-be, the oocyte. Translation of osk mRNA is repressed during its transport by several factors, including the RNA-binding protein Bruno1 (Bru1). When reaching...Axis formation of the Drosophila embryo is determined by the localized expression of specific mRNAs and proteins. This asymmetric distribution is already established during oogenesis in the mother. Oskar (Osk), which induces the formation of the posterior axis is among the first determinants to localize to the posterior pole of the egg-to-be, the oocyte. Translation of osk mRNA is repressed during its transport by several factors, including the RNA-binding protein Bruno1 (Bru1). When reaching the posterior pole, the translational repression is relieved by a yet unknown signal. In this study, we identified the highly conserved E3 ligase Makorin 1 (Mkrn1) as a novel activator of osk translation. Apart from its RING E3 ligase domain, Mkrn1 possesses C3H-type zinc finger (ZnF) domains that have been proposed to mediate the binding to RNA. Indeed, we show that Mkrn1 localizes to the posterior pole where it specifically interacts with osk 3’ UTR via its first ZnF domain. The binding is enhanced by the polyA binding protein (pAbp) that interacts with Mkrn1 via a non-consensus PAM2 motif. Furthermore, Mkrn1 interacts with several other RNA-binding proteins that regulate osk expression during oogenesis. Mechanistically, we found that Mkrn1 activates osk translation by competing with Bru1 for binding to osk 3’ UTR. Thus, we characterized Drosophila Mkrn1 as a novel and essential regulator of oogenesis. The fact that Mkrn1 shares several features with its mammalian ortholog, such as the identity of interaction partners and the dependency of pAbp for binding to RNA, suggests that the function of Mkrn1 during oogenesis might be conserved.» weiterlesen» einklappen

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DDC Sachgruppe:
Biowissenschaften, Biologie