Cohesion promotes nucleolar structure and function.

Abstract

The cohesin complex contributes to ribosome function, although the molecular mechanisms involved are unclear. Compromised cohesin function is associated with a class of diseases known as cohesinopathies. One cohesinopathy, Roberts syndrome (RBS), occurs when a mutation reduces acetylation of the cohesin Smc3 subunit. Mutation of the cohesin acetyltransferase is associated with impaired rRNA production, ribosome biogenesis, and protein synthesis in yeast and human cells. Cohesin binding to the ribosomal DNA (rDNA) is evolutionarily conserved from bacteria to human cells. We report that the RBS mutation in yeast (eco1-W216G) exhibits a disorganized nucleolus and reduced looping at the rDNA. RNA polymerase I occupancy of the genes remains normal, suggesting that recruitment is not impaired. Impaired rRNA production in the RBS mutant coincides with slower rRNA cleavage. In addition to the RBS mutation, mutations in any subunit of the cohesin ring are associated with defects in ribosome biogenesis. Depletion or artificial destruction of cohesion in a single cell cycle is associated with loss of nucleolar integrity, demonstrating that the defects at the rDNA can be directly attributed to loss of cohesion. Our results strongly suggest that organization of the rDNA provided by cohesion is critical for formation and function of the nucleolus.

• Authors: Bethany Harris, Tania Bose, Kenneth K Lee, Fei Wang, Shuai Lu, Rhonda Trimble Ross, Ying Zhang, Sarah L French, Ann L Beyer, Brian D Slaughter, Jay R Unruh, Jennifer L Gerton
• Journal: Molecular biology of the cell (Mol Biol Cell) Vol. 25 Issue 3 Pg. 337-46 (Feb 2014) ISSN: 1939-4586 [Electronic] United States
• PMID: 24307683 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• Chromatin
• Chromosomal Proteins, Non-Histone
• DNA, Ribosomal
• Nuclear Proteins
• RNA, Ribosomal
• Saccharomyces cerevisiae Proteins
• cohesins
• Acetyltransferases
• ECO1 protein, S cerevisiae
• RNA Polymerase I

Topics

• Acetyltransferases (genetics)
• Cell Cycle (genetics)
• Cell Cycle Proteins (genetics)
• Chromatin (genetics)
• Chromosomal Proteins, Non-Histone (genetics)
• Craniofacial Abnormalities (genetics)
• DNA, Ribosomal (genetics)
• Ectromelia (genetics)
• Hypertelorism (genetics)
• Microscopy, Electron, Transmission
• Mutation
• Nuclear Proteins (genetics, metabolism)
• Nucleolus Organizer Region (genetics)
• RNA Polymerase I (genetics)
• RNA, Ribosomal (biosynthesis, genetics)
• Saccharomyces cerevisiae (genetics)
• Saccharomyces cerevisiae Proteins (genetics)