Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo
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 concent...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1998
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132840/ https://www.ncbi.nlm.nih.gov/pubmed/9786943 |
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author | Misteli, Tom Cáceres, Javier F. Clement, Jade Q. Krainer, Adrian R. Wilkinson, Miles F. Spector, David L. |
author_facet | Misteli, Tom Cáceres, Javier F. Clement, Jade Q. Krainer, Adrian R. Wilkinson, Miles F. Spector, David L. |
author_sort | Misteli, Tom |
collection | PubMed |
description | 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. Cáceres, 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. |
format | Text |
id | pubmed-2132840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1998 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21328402008-05-01 Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo Misteli, Tom Cáceres, Javier F. Clement, Jade Q. Krainer, Adrian R. Wilkinson, Miles F. Spector, David L. J Cell Biol Regular Articles 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. Cáceres, 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. The Rockefeller University Press 1998-10-19 /pmc/articles/PMC2132840/ /pubmed/9786943 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Regular Articles Misteli, Tom Cáceres, Javier F. Clement, Jade Q. Krainer, Adrian R. Wilkinson, Miles F. Spector, David L. Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo |
title | Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo |
title_full | Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo |
title_fullStr | Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo |
title_full_unstemmed | Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo |
title_short | Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo |
title_sort | serine phosphorylation of sr proteins is required for their recruitment to sites of transcription in vivo |
topic | Regular Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132840/ https://www.ncbi.nlm.nih.gov/pubmed/9786943 |
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