The SON RNA splicing factor is required for intracellular trafficking that promotes centriole assembly

Abstract

Control of centrosome assembly is critical for cell division, intracellular trafficking and cilia. Regulation of centrosome number occurs through the precise duplication of centrioles that reside in centrosomes. Here we explored transcriptional control of centriole assembly and find that the RNA splicing factor SON is specifically required for completing procentriole assembly. Whole genome mRNA sequencing identified genes whose splicing and expression are affected by the reduction of SON, with an enrichment in genes involved in the microtubule cytoskeleton, centrosome and centriolar satellites. SON is required for the proper splicing and expression of CEP131 which encodes a major centriolar satellite protein and is required to organize the trafficking and microtubule network around the centrosomes. This study highlights the importance of the distinct microtubule trafficking network that is intimately associated with nascent centrioles and is responsible for procentriole development.

The ciliary impact of nonciliary gene mutations

“…Most of these genes may affect cilia via the regulation of gene expression. The splicing factor SON controls specifically the expression of various centriolar and ciliary genes [9,56,57] and was shown to affect centriole biogenesis [28]. The chromatin regulators KMT2D and ANKRD11, linked to Kabuki and KBG syndromes, respectively, were among the hits in a screen for factors involved in ciliary Hedgehog signaling [8].…”