A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm

Caceres, J. F., Screaton, G. R., Krainer, A. R. (January 1998) A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm. Genes & Development, 12 (1). pp. 55-66. ISSN 0890-9369

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Abstract

The SR proteins constitute a large family of nuclear phosphoproteins required for constitutive pre-mRNA splicing. These factors also have global, concentration-dependent effects on alternative splicing regulation and this activity is antagonized by members of the hnRNP A/B family of proteins. We show here that whereas some human SR proteins are confined to the nucleus, three of them-SF2/ASF, SRp20, and 9G8-shuttle rapidly and continuously between the nucleus and the cytoplasm. By swapping the corresponding domains between shuttling and nonshuttling SR proteins, we show that the carboxy-terminal arginine/serine-rich (RS) domain is required for shuttling. This domain, however, is not sufficient to promote shuttling of an unrelated protein reporter, suggesting that stable RNA binding mediated by the RNA-recognition motifs may be required for shuttling. Consistent with such a requirement, a double point-mutation in RRM1 of SF2/ASF that impairs RNA binding prevents the protein from shuttling. In addition, we show that phosphorylation of the RS domain affects the shuttling properties of SR proteins. These findings show that different SR proteins have unique intracellular transport properties and suggest that the family members that shuttle may have roles not only in nuclear pre-mRNA splicing but also in mRNA transport, cytoplasmic events, and/or processes that involve communication between the nucleus and the cytoplasm.

Item Type: Paper
Uncontrolled Keywords: pre-mRNA splicing SR proteins nucleocytoplasmic shuttling heterokaryons RS domain pre-messenger-rna splice-site selection hnrnp a1 in-vivo binding-proteins export domains localization transcription transport
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: January 1998
Date Deposited: 11 Dec 2013 15:39
Last Modified: 11 Dec 2013 15:39
PMCID: PMC316398
Related URLs:
URI: https://repository.cshl.edu/id/eprint/28936

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