The SON RNA splicing factor is required for intracellular trafficking structures that promote centriole assembly and ciliogenesis

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 and efficient ciliogenesis. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

Trisomy 21 induces pericentrosomal crowding delaying primary ciliogenesis and mouse cerebellar development

“…For example, MMU16 contains the splicing factor SON, which is known to splice PCNT mRNA and alters PCNT levels and distributions. 57,58 Indeed, while we do not find changes in primary cilia frequency in Dp16 animals, we do observe moderately decreased ciliary SMO and moderately increased PCNT levels. Interestingly, Dp16 mice have defects in the motile cilia lining the ependymal cells of the brain (Figure S7E-G) suggesting that elevated gene dosage can have different phenotypic consequences in different tissues.…”

“…However, there are other known cilia and centrosome genes found on HSA21, and potentially non-coding regions that may also contribute to phenotypic consequences of trisomy 21. For example, MMU16 contains the splicing factor SON, which is known to splice PCNT mRNA and alters PCNT levels and distributions ( Stemm-Wolf et al, 2021 ; Ahn et al, 2011 ). Indeed, while we do not find changes in primary cilia frequency in Dp16 animals, we do observe moderately decreased ciliary SMO and moderately increased PCNT levels.…”

New insights into the centrosome‐associated spliceosome components as regulators of ciliogenesis and tissue identity

“…For example, affinity purification followed by mass spectrometry using multiple baits from the same subcellular localization yields detailed maps of individual compartments (O'Neill et al, 2022). These methods are providing new avenues to map the intracellular localization of RNA and RNA‐binding proteins at cellular and subcellular resolution (Gupta et al, 2015; Kwon et al, 2021; O'Neill et al, 2022; Stemm‐Wolf et al, 2021; Yildirim et al, 2021). As we outline here, capturing the spatial information of RNA and RNA‐binding proteins at the subcellular level is providing new insights on the cytoplasmic roles of spliceosome components at centrosomes.…”

“…The higher requirement of EJCs for an increase in translation of mRNAs sequestered to basal bodies that are necessary for neuronal proliferation may explain the greater abundance of ribosome interaction networks in the centrosome in neurons compared to neural stem cells (O'Neill et al, 2022) (Figure 3). Similarly, the splicing factor SON, which interacts with EJC proteins as part of the mRNP complex, has been shown to be essential for centrosome assembly and ciliogenesis (Sharma et al, 2011; Singh et al, 2012; Stemm‐Wolf et al, 2021). Thus, it is becoming apparent that EJC contributes to dynamic modifications of centrosomes and cilia during neuronal differentiation.…”

Post-transcriptional and Post-translational Modifications of Primary Cilia: How to Fine Tune Your Neuronal Antenna

“…Three recent papers further cement the link between splicing factors and ciliogenesis. The splicing factor SON was reported to be required for centrosome assembly and ciliogenesis ( Stemm-Wolf et al, 2021 ). The ciliopathy protein SANS/USH1G, mutations of which lead to Usher syndrome, was shown to regulate pre mRNA splicing and interact with splicing factors SON and SF3B1 ( Yildirim et al, 2021 ).…”