SON Controls Cell-Cycle Progression by Coordinated Regulation of RNA Splicing

SummaryIt has been suspected that cell-cycle progression might be functionally coupled with RNA processing. However, little is known about the role of the precise splicing control in cell-cycle progression. Here, we report that SON, a large Ser/Arg (SR)-related protein, is a splicing cofactor contributing to efficient splicing of cell-cycle regulators. Downregulation of SON leads to severe impairment of spindle pole separation, microtubule dynamics, and genome integrity. These molecular defects result from inadequate RNA splicing of a specific set of cell-cycle-related genes that possess weak splice sites. Furthermore, we show that SON facilitates the interaction of SR proteins with RNA polymerase II and other key spliceosome components, suggesting its function in efficient cotranscriptional RNA processing. These results reveal a mechanism for controlling cell-cycle progression through SON-dependent constitutive splicing at suboptimal splice sites, with strong implications for its role in cancer and other human diseases.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (271 K)Download as PowerPoint slideHighlights► A large RS-like factor, SON, is critical for mitotic progression and genome stability ► Knockdown of SON downregulates a large set of cell-cycle-related genes ► SON is required for removal of many constitutive introns with weak splice sites ► SON facilitates SR protein-RNAP II interaction for cotranscriptional splicing