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Cajal bodies are linked to genome conformation [smallRNA-Seq]

ABSTRACT: The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. 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 chromatin 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 and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. 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 resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77915 | GEO | 2016/03/21

SECONDARY ACCESSION(S): PRJNA312099

REPOSITORIES: GEO

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Cajal bodies are linked to genome conformation [4C-Seq]

Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. 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 chromatin 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 and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. 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 resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.

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