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

Sacco-Bubulya, P. A., Spector, D. L. (2002) Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing. Journal of Cell Biology, 156 (3). pp. 425-436. ISSN 0021-9525

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URL: http://www.ncbi.nlm.nih.gov/pubmed/11827980
DOI: 10.1083/jcb.200107017

Abstract

To examine the involvement of interchromatin granule clusters (IGCs) in transcription and pre-mRNA splicing in mammalian cell nuclei, the serine-arginine (SR) protein kinase cdc2-like kinase (Clk)/STY was used as a tool to manipulate IGC integrity in vivo. Both immunofluorescence and transmission electron microscopy analyses of cells overexpressing Clk/STY indicate that IGC components are completely redistributed to a diffuse nuclear localization, leaving no residual structure. Conversely, overexpression of a catalytically inactive mutant, Clk/STY(K190R), causes retention of hypophosphorylated SR proteins in nuclear speckles. Our data suggest that the protein-protein interactions responsible for the clustering of interchromatin granules are disrupted when SR proteins are hyperphosphorylated and stabilized when SR proteins are hypophosphorylated. Interestingly, cells without intact IGCs continue to synthesize nascent transcripts. However, both the accumulation of splicing factors at sites of pre-mRNA synthesis as well as pre-mRNA splicing are dramatically reduced, demonstrating that IGC disassembly perturbs coordination between transcription and pre-mRNA splicing in mammalian cell nuclei.

Item Type: Paper
Uncontrolled Keywords: Cell Nucleus Cells, Cultured Chromatin Cytoplasmic Granules Cytoskeleton Fluorescent Antibody Technique Gene Expression Regulation, Enzymologic Green Fluorescent Proteins Humans Luminescent Proteins Microscopy, Electron Mutation Protein-Serine-Threonine Kinases Protein-Tyrosine Kinases RNA Splicing RNA, Messenger Recombinant Fusion Proteins Transcription, Genetic
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA
CSHL Authors:
Communities: CSHL labs > Spector lab
Depositing User: Matt Covey
Date Deposited: 10 Dec 2012 20:01
Last Modified: 29 Jan 2015 16:35
PMCID: PMC2173333
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26353

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