Nucleic Acids Research, 1989, Vol. 17, No. 19 7905-7921
© 1989
MOLECULAR BIOLOGY |
Nucleotide substitutions within the cardiac troponin T alternative exon disrupt pre-mRNA alternative splicing
Department of Anatomy, University of California San Francisco, CA 94143, USA
*To whom correspondence should be addressed
Received May 16, 1989. Revised June 27, 1989. Accepted August 16, 1989.
The cardiac troponin T (cTNT) prc-mRNA contains a single alternative exon (exon 5) which is either included or excluded from the processed mRNA. Using transient transfection of cTNT minigenes, we have previously localized pre-mRNA cis elements required for exon 5 alternative splicing to three small regions of the pre-mRNA which include exons 4, 5, and 6. In the present study, nucleotide substitutions were introduced into the region containing exon 5 to begin to define specific nucleotides required for exon 5 alternative splicing. A mutation within the 5' splice site flanking the cTNT alternative exon that increases its homology to the consensus sequence improves splicing efficiency and leads to increased levels of mRNAs that include the alternative exon. Surprisingly, substitution of as few as four nucleotides within the alternative exon disrupts cTNT pre-mRNA alternative splicing and prevents recognition of exon 5 as a bona fide exon. These results establish that the cTNT alternative exon contains information in cis that is required for its recognition by the splicing machinery.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. R. Bruce and M. L. Peterson Multiple features contribute to efficient constitutive splicing of an unusually large exon Nucleic Acids Res., June 1, 2001; 29(11): 2292 - 2302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Schaal and T. Maniatis Selection and Characterization of Pre-mRNA Splicing Enhancers: Identification of Novel SR Protein-Specific Enhancer Sequences Mol. Cell. Biol., March 1, 1999; 19(3): 1705 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Cooper Muscle-Specific Splicing of a Heterologous Exon Mediated by a Single Muscle-Specific Splicing Enhancer from the Cardiac Troponin T Gene Mol. Cell. Biol., August 1, 1998; 18(8): 4519 - 4525. [Abstract] [Full Text]
|
|
|
|
 |
|
 J.-D. Huang, V. Mermall, M. C. Strobel, L. B. Russell, M. S. Mooseker, N. G. Copeland, and N. A. Jenkins Molecular Genetic Dissection of Mouse Unconventional Myosin-VA: Tail Region Mutations Genetics, April 1, 1998; 148(4): 1963 - 1972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Elrick, M. B. Humphrey, T. A. Cooper, and S. M. Berget A Short Sequence within Two Purine-Rich Enhancers Determines 5' Splice Site Specificity Mol. Cell. Biol., January 1, 1998; 18(1): 343 - 352. [Abstract] [Full Text]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 P. Norton Alternative pre-mRNA splicing: factors involved in splice site selection J. Cell Sci., January 1, 1994; 107(1): 1 - 7. [PDF]
|
|
|
|
|
|
Q Sun, A Mayeda, R K Hampson, A R Krainer, and F M Rottman General splicing factor SF2/ASF promotes alternative splicing by binding to an exonic splicing enhancer. Genes & Dev., December 1, 1993; 7(12b): 2598 - 2608. [Abstract] [PDF]
|
|
|
|
|
|
A Watakabe, K Tanaka, and Y Shimura The role of exon sequences in splice site selection. Genes & Dev., March 1, 1993; 7(3): 407 - 418. [Abstract] [PDF]
|
|
|
|
|
|
W Guo, G J Mulligan, S Wormsley, and D M Helfman Alternative splicing of beta-tropomyosin pre-mRNA: cis-acting elements and cellular factors that block the use of a skeletal muscle exon in nonmuscle cells. Genes & Dev., November 1, 1991; 5(11): 2096 - 2107. [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]
|
|
|
|
 |
|
 H. Kuo, F. Nasim, and P. Grabowski Control of alternative splicing by the differential binding of U1 small nuclear ribonucleoprotein particle Science, March 1, 1991; 251(4997): 1045 - 1050. [Abstract] [PDF]
|
|
|
|
|
|
D M Helfman, R F Roscigno, G J Mulligan, L A Finn, and K S Weber Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA. Genes & Dev., January 1, 1990; 4(1): 98 - 110. [Abstract] [PDF]
|
|