Nucleotide substitutions within the cardiac troponin T alternative exon disrupt pre-mRNA alternative splicing - PubMed
- ️Sun Jan 01 1989
Nucleotide substitutions within the cardiac troponin T alternative exon disrupt pre-mRNA alternative splicing
T A Cooper et al. Nucleic Acids Res. 1989.
Free PMC article
Abstract
The cardiac troponin T (cTNT) pre-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.
Similar articles
-
Cis requirements for alternative splicing of the cardiac troponin T pre-mRNA.
Cooper TA, Cardone MH, Ordahl CP. Cooper TA, et al. Nucleic Acids Res. 1988 Sep 12;16(17):8443-65. doi: 10.1093/nar/16.17.8443. Nucleic Acids Res. 1988. PMID: 3419923 Free PMC article.
-
The cardiac troponin T alternative exon contains a novel purine-rich positive splicing element.
Xu R, Teng J, Cooper TA. Xu R, et al. Mol Cell Biol. 1993 Jun;13(6):3660-74. doi: 10.1128/mcb.13.6.3660-3674.1993. Mol Cell Biol. 1993. PMID: 8388541 Free PMC article.
-
Exon identity crisis: disease-causing mutations that disrupt the splicing code.
Sterne-Weiler T, Sanford JR. Sterne-Weiler T, et al. Genome Biol. 2014 Jan 23;15(1):201. doi: 10.1186/gb4150. Genome Biol. 2014. PMID: 24456648 Free PMC article. Review.
-
[Splice site mutations and atherosclerosis: mechanisms and prediction models].
von Kodolitsch Y, Nienaber CA, Fliegner M, Rogan PK. von Kodolitsch Y, et al. Z Kardiol. 2001 Feb;90(2):87-95. doi: 10.1007/s003920170193. Z Kardiol. 2001. PMID: 11263007 Review. German.
Cited by
-
mRNA Metabolism in Cardiac Development and Disease: Life After Transcription.
Gao C, Wang Y. Gao C, et al. Physiol Rev. 2020 Apr 1;100(2):673-694. doi: 10.1152/physrev.00007.2019. Epub 2019 Nov 21. Physiol Rev. 2020. PMID: 31751167 Free PMC article. Review.
-
Krishan K, Morgan MJ, Zhao W, Dhoot GK. Krishan K, et al. J Muscle Res Cell Motil. 2000;21(6):527-36. doi: 10.1023/a:1026541803317. J Muscle Res Cell Motil. 2000. PMID: 11206131
-
Multiple features contribute to efficient constitutive splicing of an unusually large exon.
Bruce SR, Peterson ML. Bruce SR, et al. Nucleic Acids Res. 2001 Jun 1;29(11):2292-302. doi: 10.1093/nar/29.11.2292. Nucleic Acids Res. 2001. PMID: 11376148 Free PMC article.
-
3' splice site selection in dicot plant nuclei is position dependent.
Lou H, McCullough AJ, Schuler MA. Lou H, et al. Mol Cell Biol. 1993 Aug;13(8):4485-93. doi: 10.1128/mcb.13.8.4485-4493.1993. Mol Cell Biol. 1993. PMID: 8336697 Free PMC article.
-
Andreadis A, Broderick JA, Kosik KS. Andreadis A, et al. Nucleic Acids Res. 1995 Sep 11;23(17):3585-93. doi: 10.1093/nar/23.17.3585. Nucleic Acids Res. 1995. PMID: 7567473 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials