Cajal bodies are linked to genome conformation

Qiuyan Wang, Iain A. Sawyer, Myong-Hee Sung, David Sturgill, Sergey P. Shevtsov, Gianluca Pegoraro, Ofir Hakim, Songjoon Baek, Gordon L. Hager () and Miroslav Dundr ()
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Qiuyan Wang: Rosalind Franklin University of Medicine and Science, Chicago Medical School
Iain A. Sawyer: Rosalind Franklin University of Medicine and Science, Chicago Medical School
Myong-Hee Sung: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health
David Sturgill: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Sergey P. Shevtsov: Rosalind Franklin University of Medicine and Science, Chicago Medical School
Gianluca Pegoraro: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Ofir Hakim: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Songjoon Baek: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Gordon L. Hager: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Miroslav Dundr: Rosalind Franklin University of Medicine and Science, Chicago Medical School

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: Abstract The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. Here we examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromosome conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear or nucleolar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. In particular, we observed a number of CB-dependent gene-positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production results in increased splicing noise, even in CB-distal regions. Therefore, we conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.

Date: 2016
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DOI: 10.1038/ncomms10966

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