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

Control of the number of centrosomes is critical for cell division, trafficking and cilia. Regulation of centrosome number occurs through the precise duplication of centrioles that reside in the center of centrosomes. Here we explored transcriptional control of centriole assembly by focusing on alternative splicing factors in isolation from other cell cycle processes. Of five splicing factors originally identified as required for centriole assembly, only SON is specifically required. Procentriole assembly is severely disrupted when SON is reduced but early centriole assembly events still occur. Whole genome mRNA sequencing identified thousands of genes whose splicing and expression are affected by the reduction of SON, with an enrichment of genes involved in the microtubule cytoskeleton. SON is required for the proper splicing and expression of the centriolar satellite protein, CEP131. Fluorescence microscopy and electron tomography establish key differences to the trafficking and microtubule network around the centrosomes that contribute to the centriole assembly defects. This establishes SON as required for centriole assembly, partially through its activity in splicing CEP131 and through control of microtubules organized by the centrosome. Overall design: Analysis of changes in mRNA abundance and alternative splicing after knockdown of the human splicing factor SON.