c entrocortin RNA localization to centrosomes is regulated by FMRP and facilitates error-free mitosis

Abstract

Centrosomes are microtubule-organizing centers required for error-free mitosis and embryonic development. The microtubule-nucleating activity of centrosomes is conferred by the pericentriolar material (PCM), a composite of numerous proteins subject to cell cycle–dependent oscillations in levels and organization. In diverse cell types, mRNAs localize to centrosomes and may contribute to changes in PCM abundance. Here, we investigate the regulation of mRNA localization to centrosomes in the rapidly cycling Drosophila melanogaster embryo. We find that RNA localization to centrosomes is regulated during the cell cycle and developmentally. We identify a novel role for the fragile-X mental retardation protein in the posttranscriptional regulation of a model centrosomal mRNA, centrocortin (cen). Further, mistargeting cen mRNA is sufficient to alter cognate protein localization to centrosomes and impair spindle morphogenesis and genome stability.

mRNA Targeting, Transport and Local Translation in Eukaryotic Cells: From the Classical View to a Diversity of New Concepts

“…It is only known that during cell division, some mRNAs are directed along microtubules into the pericentriole matrix, and then redistributed between daughter cells via actin transport, thus providing asymmetric segregation of transcripts [ 261 ]. Disruption of the centrosomal localization of only one mRNA ( cen ) leads to errors in the assembly of the division spindle and genome instability in the drosophila embryo model [ 262 ]. It is interesting that the synthesis of a number of proteins of the centrosomes also occurs directly on these organelles, which is due to the product-dependent localization of the corresponding mRNA [ 263 ].…”

Think globally, act locally: Centrosome-localized mRNAs ensure mitotic fidelity

“…(c) What is the functional significance of mRNA localization to centrosomes throughout development and in different cell types? In this issue, Ryder et al address these questions to shed light on the functional significance of mRNA localization to centrosomes (7).…”

“…The latter could be explained by the mother centrosome having a larger PCM with a higher content of Cnn scaffolding protein. Ryder et al performed the majority of their analyses at nuclear cycle (NC) 13, which has a longer interphase that facilitates sample acquisition (7). When visualized at stage NC 10, cen mRNA granules were not detected, suggesting distinct mechanisms of mRNA localization and assembly with the centrosome during development.…”

“…Using a combination of immunofluorescence and genetics, they found that when Cnn-Cen protein interactions are disrupted in the mutant cnn B4 , cen mRNA granules were no longer detected. Surprisingly, Cen protein levels remained unchanged, and Ryder et al found that cen mRNA granules were not required for steady-state levels of Cen (7). While the authors suggested that the effect of cen mRNA granule loss could be confounded by maternal Cen deposition, it is also possible that Cen protein levels remain unchanged due to protein degradation and translation cancelling each other out in the context of the cnn B4 mutation.…”

“…What is the functional significance of mRNA localization to centrosomes throughout development and in different cell types? Ryder et al set out to investigate the functional consequences of cen mRNA mistargeting in Drosophila embryos (7). They generated chimeric c9UTR transgenes that target cen mRNA to the anterior pole while depleting it from the middle of the embryo.…”