Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo

Misteli, T., Cáceres, J. F., Clement, J. Q., Krainer, A. R., Wilkinson, M. F., Spector, D. L. (1998) Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo. Journal of Cell Biology, 143 (2). pp. 297-307. ISSN 0021-9525

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URL: http://www.ncbi.nlm.nih.gov/pubmed/9786943
DOI: 10.1083/jcb.143.2.297

Abstract

Expression of most RNA polymerase II transcripts requires the coordinated execution of transcription, splicing, and 3' processing. We have previously shown that upon transcriptional activation of a gene in vivo, pre-mRNA splicing factors are recruited from nuclear speckles, in which they are concentrated, to sites of transcription (Misteli, T., J.F. Caceres, and D.L. Spector. 1997. Nature. 387:523-527). This recruitment process appears to spatially coordinate transcription and pre-mRNA splicing within the cell nucleus. Here we have investigated the molecular basis for recruitment by analyzing the recruitment properties of mutant splicing factors. We show that multiple protein domains are required for efficient recruitment of SR proteins from nuclear speckles to nascent RNA. The two types of modular domains found in the splicing factor SF2/ ASF exert distinct functions in this process. In living cells, the RS domain functions in the dissociation of the protein from speckles, and phosphorylation of serine residues in the RS domain is a prerequisite for this event. The RNA binding domains play a role in the association of splicing factors with the target RNA. These observations identify a novel in vivo role for the RS domain of SR proteins and suggest a model in which protein phosphorylation is instrumental for the recruitment of these proteins to active sites of transcription in vivo.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Gene Deletion HeLa Cells Humans Molecular Sequence Data Mutagenesis Nuclear Proteins Phosphoproteins Phosphorylation RNA Precursors RNA Splicing RNA-Binding Proteins Serine Transcription, Genetic
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > SR proteins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression
CSHL Authors:
Communities: CSHL labs > Krainer lab
CSHL labs > Spector lab
Depositing User: Matt Covey
Date Deposited: 10 Dec 2012 19:56
Last Modified: 29 Jan 2015 17:23
PMCID: PMC2132840
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26342

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