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, Miroslav Dundr

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

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.

Original languageEnglish
Article number10966
JournalNature Communications
Volume7
DOIs
StatePublished - 21 Mar 2016

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