Regulation of Alternative Splicing by SRrp86 and Its Interacting Proteins

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2003 Oct 16

PMID 14559993

Citations 19

Authors

Jun Li

Ian C Hawkins

Christopher D Harvey

Jennifer L Jennings

Andrew J Link

James G Patton

Affiliations

Soon will be listed here.

Abstract

SRrp86 is a unique member of the SR protein superfamily containing one RNA recognition motif and two serine-arginine (SR)-rich domains separated by an unusual glutamic acid-lysine (EK)-rich region. Previously, we showed that SRrp86 could regulate alternative splicing by both positively and negatively modulating the activity of other SR proteins and that the unique EK domain could inhibit both constitutive and alternative splicing. These functions were most consistent with the model in which SRrp86 functions by interacting with and thereby modulating the activity of target proteins. To identify the specific proteins that interact with SRrp86, we used a yeast two-hybrid library screen and immunoprecipitation coupled to mass spectrometry. We show that SRrp86 interacts with all of the core SR proteins, as well as a subset of other splicing regulatory proteins, including SAF-B, hnRNP G, YB-1, and p72. In contrast to previous results that showed activation of SRp20 by SRrp86, we now show that SAF-B, hnRNP G, and 9G8 all antagonize the activity of SRrp86. Overall, we conclude that not only does SRrp86 regulate SR protein activity but that it is, in turn, regulated by other splicing factors to control alternative splice site selection.

Citing Articles

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The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma.

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Role of Y Box Protein-1 in cancer: As potential biomarker and novel therapeutic target.

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The RNA-binding landscape of RBM10 and its role in alternative splicing regulation in models of mouse early development.

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