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J Biol Chem, Vol. 274, Issue 42, 29838-29842, October 15, 1999
The Relative Strengths of SR Protein-mediated Associations of
Alternative and Constitutive Exons Can Influence Alternative
Splicing
Jeremy M.
Stark ,
Thomas A.
Cooper¶, and
Mark B.
Roth
From the Division of Basic Sciences and Molecular and
Cellular Biology Program, Fred Hutchinson Cancer Research Center,
Seattle, Washington 98104 and the ¶ Departments of Pathology and
Cell Biology, Baylor College of Medicine, Houston, Texas 77030
We have characterized the functional role of SR
protein-mediated exon/exon associations in the alternative splicing of
exon 5 of chicken cardiac troponin T (cTnT). We have previously shown that SR proteins can promote the association of the alternative exon 5 with the flanking constitutive exon 6 of this pre-mRNA. In this
study, we have shown that when exons 2, 3, and 4 of the cTnT
pre-mRNA are spliced together, the composite exon 2/3/4 contains an
additional SR protein binding site. Furthermore, we have found that SR
proteins can also promote interactions between the pairs of exons
2/3/4-5 and 2/3/4-6. We then asked whether the SR protein binding sites
in these exons play a role in cTnT alternative splicing in
vivo. We found that the SR protein binding sites in exons 2/3/4 and 6 promote exon 5 skipping, and it has previously been shown that
the SR protein binding site in exon 5 promotes exon 5 inclusion. Consistent with these results, we find that the SR protein-mediated association of exon 2/3/4 with 6 is preferred over associations involving exon 5, in that exons 2/3/4 and 6 are more efficient than
exon 5 in competing an SR protein-mediated exon/exon association. We
suggest that the relative strengths of SR protein-mediated associations
of alternative and constitutive exons play a role in determining
alternative splicing patterns.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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