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Calcitonin Exon Sequences Influence Alternative RNA Processing

Department of Medicine, Veterans Administration Medical Center and Baylor College of Medicine Houston, Texas 77030
Department of Biochemistry, Veterans Administration Medical Center and Baylor College of Medicine Houston, Texas 77030
Department of cell Biology, Veterans Administration Medical Center and Baylor College of Medicine Houston, Texas 77030

Address requests for reprints to: Robert F. Gagel, M.D., Veterans Administration Medical Center 111E, Laboratory of Molecular and Cellular Endocrinology, 2002 Holcombe Boulevard, Houston, Texas 77030.

Abstract

The pre-mRNA encoding calcitonin (CT) and CT gene-related peptide (CGRP) is differentially processed in a tissue-specific fashion to include exon 4 (which encodes CT) or exclude this exon and splice to exon 5 (which encodes CGRP). We have used a CT-specific in vitro RNA-processing system to identify cis-acting sequences required to prevent splicing to exon 5. Deletion mapping demonstrated the presence of an element within the first 45 nucleotides of the CT-specific exon 4 that was required to suppress splicing to the CGRP-specific exon 5. This element was able to function in a completely heterologous system to suppress splicing when the CGRP exon was replaced with a constitutive viral exon. The element was unable to suppress splicing in the absence of a proximal CT-specific 3' splice site. Our results suggest that CT-specific splicing requires assisted recognition of its 3' splice site.

FOOTNOTES

This work was supported by USPHS Grants DK-38146 (to R.F.G.) and GM-35670 (to S.M.B.), and a V.A. Career Development Award (to R.F.G.).

Received for publication July 13, 1990. Revision received August 14, 1990. Accepted for publication August 14, 1990.

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