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Abstract Messenger RNAs (mRNAs) accumulate at centrosomes in mitosis and interphase, yet the mechanisms governing their localization and the functional significance of centrosomal localization remain poorly understood. Here, we investigate the regulation and function of the centrosome-localized mRNA, CEP350 . We find that CEP350 mRNA localizes to centrosomes during S phase via the centriolar satellite protein CEP131 and the RNA binding protein (RBP) Unkempt (UNK), in a microtubule (MT)-dependent manner. CEP131 and UNK stabilize CEP350 mRNA to maintain CEP350 mRNA steady-state levels. Furthermore, CEP131 and UNK promote normal CEP350 protein levels at centrosomes. CEP350 is required for PLK4-induced centriole overduplication but is less important for canonical centriole duplication. Moreover, CEP131, UNK, and CEP350 are important for centrosome amplification in triple-negative breast cancer cells. Together, these findings reveal a centriolar satellite-RBP pathway regulating CEP350 mRNA localization to centrosomes. Significance Statement mRNAs encoding centrosomal proteins localize to centrosomes during interphase, though the mechanism and functional significance of this localization remains unclear. This study finds that the centriolar satellite proteins CEP131 and UNK regulate centrosomal localization of CEP350 mRNA and protein during S phase. CEP131, UNK, and CEP350 are required for centrosome amplification in triple negative breast cancer cells – a dependency that identifies them as potential therapeutic targets.
Martinez et al. (Fri,) studied this question.