Multiple Distinct Splicing Enhancers in the Protein-Coding Sequences of a Constitutively Spliced Pre-mRNA

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Molecular and Cellular Biology, January 1999, p. 261-273, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Multiple Distinct Splicing Enhancers in the Protein-Coding Sequences of a Constitutively Spliced Pre-mRNA

Thomas D. Schaal and Tom Maniatis^*

Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138

Received 29 July 1998/Returned for modification 16 September 1998/Accepted 28 September 1998

We have identified multiple distinct splicing enhancer elements within protein-coding sequences of the constitutively splicedhuman $beta$ -globin pre-mRNA. Each of these highly conserved sequencesis sufficient to activate the splicing of a heterologous enhancer-dependentpre-mRNA. One of these enhancers is activated by and binds tothe SR protein SC35, whereas at least two others are activatedby the SR protein SF2/ASF. A single base mutation within anotherenhancer element inactivates the enhancer but does not changethe encoded amino acid. Thus, overlapping protein coding and RNArecognition elements may be coselected during evolution. Thesestudies provide the first direct evidence that SR protein-specificsplicing enhancers are located within the coding regions of constitutivelyspliced pre-mRNAs. We propose that these enhancers function asmultisite splicing enhancers to specify 3' splice-siteselection.

^* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Ave.,Cambridge, MA 02138. Phone: (617) 495-1811. Fax: (617) 495-3537.E-mail: maniatis{at}biohp.harvard.edu.

Molecular and Cellular Biology, January 1999, p. 261-273, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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