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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164278 | GEO | 2021/12/22

REPOSITORIES: GEO

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

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

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SON and its alternatively spliced isoforms control MLL complex-mediated H3K4me3 and transcription of leukemia-associated genes (ChIP-seq data)

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Son Maintains Accurate Splicing of Pre-mRNAs Encoding Chromatin Modifiers

Project description:Exon and expression analysis of HeLa cells after knockdown of SON Serine-arginine-rich (SR) proteins play a key role in alternative pre-mRNA splicing in eukaryotes. Our laboratory recently showed that a large SR protein called Son has unique repeat motifs that are essential for maintaining the subnuclear organization of pre-mRNA processing factors in nuclear speckles. Motif analysis of Son highlights putative RNA interaction domains that suggest a direct role for Son in pre-mRNA splicing. A genome-wide screen was performed to identify putative human transcription and splicing targets of Son.

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Son Maintains Accurate Splicing of Pre-mRNAs Encoding Chromatin Modifiers

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RNA-Seq after knockdown of SON in human embryonic stem cells

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Project description:Centriole biogenesis and maintenance are crucial for cells to generate cilia and assemble centrosomes that function as microtubule organizing centers (MTOCs). Centriole biogenesis and MTOC function both require the microtubule nucleator -tubulin ring complex (TuRC). It is widely accepted that TuRC nucleates microtubules from the pericentriolar material (PCM) that is associated with the proximal part of centrioles. However, TuRC also localizes more distally and in the centriole lumen, but the significance of these findings is unclear. Here we identify spatially and functionally distinct sub-populations of centrosomal TuRC. Luminal localization is mediated by augmin, which is linked to the centriole inner scaffold through POC5. Disruption of luminal localization impairs centriole integrity and interferes with cilium assembly. Defective ciliogenesis is also observed in TuRC mutant fibroblasts from a patient suffering from microcephaly with chorioretinopathy. These results identify a novel, non-canonical role of augmin-γTuRC in the centriole lumen that is linked to human disease.

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