Regulation of alternative splicing by SRrp86 and its interacting proteins.

Li J, Hawkins IC, Harvey CD, Jennings JL, Link AJ, Patton JG
Mol Cell Biol. 2003 23 (21): 7437-47

PMID: 14559993 · PMCID: PMC207616 · DOI:10.1128/mcb.23.21.7437-7447.2003

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.

MeSH Terms (25)

Adenosine Triphosphatases Alternative Splicing Animals Carrier Proteins CCAAT-Enhancer-Binding Proteins Cell Line DEAD-box RNA Helicases DNA-Binding Proteins Heterogeneous-Nuclear Ribonucleoproteins Humans Matrix Attachment Region Binding Proteins Mice NFI Transcription Factors Nuclear Matrix-Associated Proteins Nuclear Proteins Nucleocytoplasmic Transport Proteins Protein Binding Receptors, Estrogen RNA, Messenger RNA-Binding Proteins RNA Helicases Serine-Arginine Splicing Factors Transcription Factors Two-Hybrid System Techniques Y-Box-Binding Protein 1

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