title: SON controls cell-cycle progression by coordinated regulation of RNA splicing.
abstract: It 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.
authors.affiliation: Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Ahn
authors.forename: Russell C
authors.initials: RC
authors.lastname: DeKelver
authors.forename: Miao-Chia
authors.initials: MC
authors.lastname: Lo
authors.forename: Tuyet Ann
authors.initials: TA
authors.lastname: Nguyen
authors.forename: Shinobu
authors.initials: S
authors.lastname: Matsuura
authors.forename: Anita
authors.initials: A
authors.lastname: Boyapati
authors.forename: Shatakshi
authors.initials: S
authors.lastname: Pandit
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
authors.forename: Dong-Er
authors.initials: DE
authors.lastname: Zhang
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D020090:Chromosome Segregation; D048749:Cytokinesis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018816:Genes, cdc; D042822:Genomic Instability; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008870:Microtubules / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D012326:RNA Splicing; D008941:Spindle Apparatus / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; C088203:SON protein, human; D012319:RNA Polymerase II