Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing

doi:10.1083/jcb.200107017

Published 4 February 2002. doi:10.1083/jcb.200107017

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© The Rockefeller University Press, 0021-9525/2002/2/425 $5.00
The Journal of Cell Biology, Volume 156, Number 3, February 4, 2002 425-436

Article

Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing

Paula Sacco-Bubulya and David L. Spector

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724

Address correspondence to David L. Spector, Cold Spring Harbor Laboratory, 1 Bungtown Rd., Cold Spring Harbor, NY 11724. Tel.: (516) 367-8456. Fax: (516) 367-8876. E-mail: spector{at}cshl.org

To examine the involvement of interchromatin granule clusters(IGCs) in transcription and pre-mRNA splicing in mammalian cellnuclei, the serine-arginine (SR) protein kinase cdc2-like kinase(Clk)/STY was used as a tool to manipulate IGC integrity invivo. Both immunofluorescence and transmission electron microscopyanalyses of cells overexpressing Clk/STY indicate that IGC componentsare completely redistributed to a diffuse nuclear localization,leaving no residual structure. Conversely, overexpression ofa catalytically inactive mutant, Clk/STY(K190R), causes retentionof hypophosphorylated SR proteins in nuclear speckles. Our datasuggest that the protein–protein interactions responsiblefor the clustering of interchromatin granules are disruptedwhen SR proteins are hyperphosphorylated and stabilized whenSR proteins are hypophosphorylated. Interestingly, cells withoutintact IGCs continue to synthesize nascent transcripts. However,both the accumulation of splicing factors at sites of pre-mRNAsynthesis as well as pre-mRNA splicing are dramatically reduced,demonstrating that IGC disassembly perturbs coordination betweentranscription and pre-mRNA splicing in mammalian cell nuclei.

Key Words: interchromatin granule cluster; transcription; pre-mRNA splicing; Clk/STY; nucleus

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