Nucleic Acids Research, 1989, Vol. 17, No. 3 925-938
© 1989
MOLECULAR BIOLOGY |
Role of the branch site/3'-splice site region in adenovirus-2 E1A pre-mRNA alternative splicing: evidence for 5'- and 3'-splice site co-operation
1Department of Medical Genetics, BMC Box 589, S-751 23 Uppsala 2Department of Microbial Genetics, Medical Nobel Institute, Karolinska Institute Box 60400, S-104 01 Stockholm, Sweden
Received November 23, 1988. Accepted January 3, 1989.
The adenovirus E1A gene encodes five overlapping mRNAs which are processed by alternative RNA splicing from a common pre-mRNA. To characterize cis-acting sequence elements which are of importance for the alternative 5'-splice site selection deletion and substitution mutants within the intron that is common to all E1A mRNAs were constructed. Deletion of the wild-type E1A branch site/polypyrimidine tract resulted in activation of a functionally redundant sequence located within an A/T rich sequence just upstream of the normal E1A lariat branch site. Removal of both regulatory sequences abolished in vivo splicing completely and did not lead to activation of cryptic 3'-splice sites at other locations in the ElA pre-mRNA. Furthermore we show that the sequence around the E1A branch site/3'-splice site region may have a more direct effect on the efficiency by which the alternative E1A 5'-splice sites are selected. Replacing the E1A branch siteß'-splice site region with the corresponding sequence from the second intron of the rabbit ß-globin gene or the first intron of the major late transcription unit resulted in drastic changes in E1A 5'-splice site selection. For example, with the E1A/ß-globin hybrid gene the 9S mRNA became the most abundant E1A mRNA to accumulate. This contrasts with the wild-type E1A gene in which almost undetectable levels of 9S mRNA were produced in transient expression assays. Our results strongly suggest that a cooperative interaction between 5'- and 3'-splice sites on a pre-mRNA determines the outcome of alternative splicing.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Gersappe and D. J. Pintel CA- and Purine-Rich Elements Form a Novel Bipartite Exon Enhancer Which Governs Inclusion of the Minute Virus of Mice NS2-Specific Exon in Both Singly and Doubly Spliced mRNAs Mol. Cell. Biol., January 1, 1999; 19(1): 364 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G S Huh and R O Hynes Regulation of alternative pre-mRNA splicing by a novel repeated hexanucleotide element. Genes & Dev., July 1, 1994; 8(13): 1561 - 1574. [Abstract] [PDF]
|
|
|
|
|
|
R Gattoni, K Chebli, M Himmelspach, and J Stevenin Modulation of alternative splicing of adenoviral E1A transcripts: factors involved in the early-to-late transition. Genes & Dev., October 1, 1991; 5(10): 1847 - 1858. [Abstract] [PDF]
|
|
|
|
|
|
D L Black Does steric interference between splice sites block the splicing of a short c-src neuron-specific exon in non-neuronal cells? Genes & Dev., March 1, 1991; 5(3): 389 - 402. [Abstract] [PDF]
|
|
|
|
|
|
Y Zhuang and A M Weiner A compensatory base change in human U2 snRNA can suppress a branch site mutation. Genes & Dev., October 1, 1989; 3(10): 1545 - 1552. [Abstract] [PDF]
|
|
|
|
 |
|
 H. S. Hummel, R. D. Gillespie, and J. Swindle Mutational Analysis of 3' Splice Site Selection during trans-Splicing J. Biol. Chem., November 3, 2000; 275(45): 35522 - 35531. [Abstract] [Full Text] [PDF]
|
|