Document Detail

SON controls cell-cycle progression by coordinated regulation of RNA splicing.
MedLine Citation:
PMID:  21504830     Owner:  NLM     Status:  MEDLINE    
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.
Eun-Young Ahn; Russell C DeKelver; Miao-Chia Lo; Tuyet Ann Nguyen; Shinobu Matsuura; Anita Boyapati; Shatakshi Pandit; Xiang-Dong Fu; Dong-Er Zhang
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cell     Volume:  42     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-20     Completed Date:  2011-06-17     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  185-98     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Cell Cycle / genetics*
Chromosome Segregation
DNA-Binding Proteins / genetics,  metabolism*
Genes, cdc*
Genomic Instability
HEK293 Cells
HeLa Cells
K562 Cells
Microtubules / metabolism
RNA Interference
RNA Polymerase II / metabolism
RNA Splicing*
Spindle Apparatus / metabolism
Spliceosomes / metabolism*
Time Factors
Grant Support
CA096735/CA/NCI NIH HHS; CA104509/CA/NCI NIH HHS; F32 HL091641/HL/NHLBI NIH HHS; GM049369/GM/NIGMS NIH HHS; R01 CA096735/CA/NCI NIH HHS; R01 CA096735-07A1/CA/NCI NIH HHS; R01 CA096735-08/CA/NCI NIH HHS; R01 CA096735-09/CA/NCI NIH HHS; R01 CA096735-10/CA/NCI NIH HHS; R01 GM049369/GM/NIGMS NIH HHS; R01 GM049369-16/GM/NIGMS NIH HHS; R01 GM049369-17/GM/NIGMS NIH HHS; R01 HG004659/HG/NHGRI NIH HHS
Reg. No./Substance:
0/DNA-Binding Proteins; 0/SON protein, human; EC 2.7.7.-/RNA Polymerase II

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