Abstract
ALTERNATIVE splicing of eukaryotic messenger RNA precursors represents a common mechanism for generating multiple transcripts from a single gene1,2. Although there has been increasing information concerning the sequence requirements and the biochemical mechanisms involved in the constitutive splicing of primary RNA transcripts, very little is known about the sequences or mechanisms which determine alternative RNA-processing events in complex transcription units3–6. The calcitonin/calcitonin gene-related peptide (CGRP) primary RNA transcript undergoes tissue-specific alternative processing, resulting in the differential production of calcitonin mRNA in thyroid C cells and CGRP mRNA in neurons of the central and peripheral nervous systems7,8. To elucidate the molecular mechanisms underlying these alternative RNA processing events, we have examined the nucleotide sequences involved in the production of calcitonin and CGRP mRNAs. Analyses of HeLa and F9 cell lines transfected with a variety of mutant calcitonin/CGRP transcription units have demonstrated that alternative splice-site selection is primarily regulated by cis-active element(s) near the calcitonin-specific 3′-splice junction. We suggest that the tissue-specific pattern of alternative RNA processing is conferred by sequence information at the calcitonin-specific acceptor which serves to inhibit the production of calcitonin transcripts in CGRP-producing cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Breitbart, R. E., Andreadis, A. & Nadal-Ginard, B. A. Rev. Biochem. 56, 467–495 (1987).
Leff, S. E., Rosenfeld M. G. & Evans, R. M. A. Rev. Biochem. 55, 1091–1117 (1986).
Padgett, R. A., Grabowski, P. J., Konarska, M. M., Seiler, S. & Sharp, P. A. A. Rev. Biochem. 55, 1119–1150 (1986).
Guthrie, C. & Patterson, B. A. Rev. Genet. 22, 387–419 (1988).
Cheng, S. C. & Abelson, J. Genes Dev. 1, 1014–1027 (1987).
Steitz, J. A. et al. Structure and Function of Major and Minor SnRNPs (ed. Birnstiel, M. L.) 115–154 (Springer, Heidelberg, 1988).
Amara, S. G., Jonas, V., Rosenfeld, M. G., Ong, E. S. & Evans, R. M. Nature 298, 240–244 (1982).
Sabate, M. I. et al. J. biol. Chem. 260, 2589–2592 (1985).
Amara, S. G., Evans, R. M. & Rosenfeld, M. G. Mol. cell. Biol. 4, 2151–2160 (1984).
Crenshaw, E. B., Russo, A. F., Swanson, L. W. & Rosenfeld, M. G. Cell 49, 389–398 (1987).
Leff, S. E., Evans, R. M. & Rosenfeld, M. G. Cell 48, 517–524 (1987).
Bovenberg, R. A. L. et al. Nucleic Acids Res. 14, 8785–8803 (1986).
Bovenberg, R. A. L., Adema, G. J., Jansz, H. S., Baas, P. D. Nucleic Acids Res. 16, 7867–7883 (1988).
Reed, R. & Maniatis, T. Genes and Dev. 2, 1268–1276 (1988).
Konarska, M. M., Grabowski, P. J., Padgett, R. A. & Sharp, P. A. Nature 313, 552–557 (1985).
Weiringa, B., Meyer, F., Reiser, J. & Weissmann, C. Nature 301, 38–43 (1983).
Smith, C. W. J. & Nadal-Ginard, B. Cell 56, 749–758 (1989).
Mount, S. M. Nucleic Acids Res. 10, 459–472 (1982).
Boggs, R. T., Gregor, P., Idriss, S., Belote, J. M. & McKeown, M. Cell 50, 739–747 (1987).
Goralski, T. J., Edstrom, J-E. & Baker, B. S. Cell 56, 1011–1018 (1989).
Bell, L. R., Maine, E. M., Schedl, P. & Cline, T. W. Cell 55, 1037–1046 (1988).
Bandziulis, R. J., Swanson, M. S. & Dreyfuss, G. Genes Dev. 3, 431–437 (1989).
Laski, F. A. & Rubin, G. H. Genes Dev. 3, 720–728 (1989).
Streuli, M. & Saito, H. EMBO J. 8, 787–796 (1989).
Chen, C. & Okayama, H. Molec. cell. Biol. 7, 2745–2752 (1987).
MacDonald, R. J., Swift, G. H., Przybyla, A. E. & Chirgwin, J. M. Meth. Enzym. 152, 219–227 (1987).
Ausubel, F. M. et al. (eds) Current Protocols in Molecular Biology (Wiley, New York, 1989).
Kunkel, T. A. Proc. natn. Acad. Sci. U.S.A. 82, 488–492 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Emeson, R., Hedjran, F., Yeakley, J. et al. Alternative production of calcitonin and CGRP mRNA is regulated at the calcitonin-specific splice acceptor. Nature 341, 76–80 (1989). https://doi.org/10.1038/341076a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/341076a0
This article is cited by
-
Neuropeptides as a Marker for Chronic Headache
Current Pain and Headache Reports (2017)
-
Monoclonal Antibodies for Migraine: Preventing Calcitonin Gene-Related Peptide Activity
CNS Drugs (2014)
-
Protective Roles of α-Calcitonin and β-Calcitonin Gene-Related Peptide in Spontaneous and Experimentally Induced Colitis
Digestive Diseases and Sciences (2008)
-
Regulation of alternative splicing by RNA editing
Nature (1999)
-
Modulation of preoptic regulatory factor-2 (porf-2) mRNAs by castration and hypophysectomy
Endocrine (1997)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.