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Centrocortin potentiates co-translational localization of its mRNA to the centrosome via dynein

Hala Zein-SabattoiD, Jovan S. BrockettiD, Li JiniD, Christian A. Husbands, Jina LeeiD, Junnan FangiD, Joseph BuehleriD, Simon L. BullockiD, Dorothy A. LeritiD

Abstract

Centrosomes rely upon proteins within the pericentriolar material to nucleate and organize microtubules. Several mRNAs also reside at centrosomes, although less is known about how and why they accumulate there. We previously showed that local Centrocortin (Cen) mRNA supports centrosome separation, microtubule organization, and viability in Drosophila embryos. Here, using Cen mRNA as a model, we examine mechanisms of centrosomal mRNA localization. We find that while the Cen N-terminus is sufficient for protein enrichment at centrosomes, multiple domains cooperate to concentrate Cen mRNA at this location. We further identify an N-terminal motif within Cen that is conserved among dynein cargo adaptor proteins and test its contribution to RNA localization. Our results support a model whereby Cen protein enables the accumulation of its own mRNA to centrosomes through a mechanism requiring active translation, microtubules, and the dynein motor complex. Taken together, our data uncover the basis of translation-dependent localization of a centrosomal RNA required for mitotic integrity. SummaryEnrichment of Centrocortin (Cen) mRNA at centrosomes is required for mitotic fidelity. This study describes a mechanism underlying co-translational Cen mRNA targeting involving microtubules, the dynein motor, and a highly conserved dynein binding motif within the Cen coding sequence.

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