Abstract
The primary sequences of four molecular mass variants (14, 17, 18.5, and 21.5 kDa) of the mouse myelin basic protein (MBP) have recently been determined through analysis of cDNA clones of their mRNAs. The mRNAs coding for the four MBP variants are thought to arise by differential splicing of two exons (exons 2 and 6) from a single gene. In contrast, exons 2 and 5 may be spliced out in the posttranscriptional processing of the human MBP gene. To investigate the possibility that a third exon (exon 5) may also be differentially spliced out in the processing of the mouse MBP gene transcript, a mouse cDNA library was screened to search for cDNAs missing exon 5. A MBP cDNA was isolated whose coding region specified a fifth mouse MBP variant with a molecular mass of approximately equal to 17 kDa. The mass of this variant (17,257 Da) is so close to that of the other 17-kDa mouse MBP (17,224 Da) that the two would be indistinguishable on NaDodSO4/polyacrylamide gels. Analysis of the sequence of the cDNA clone indicates that excision of exons 2 and 5 of the mouse MBP gene would produce the mRNA encoding this newly described 17-kDa MBP, whereas excision of exon 6 would produce the mRNA for the other 17-kDa MBP variant. Thus, the "17-kDa" mouse MBP consists of at least two molecular forms with very similar molecular masses but markedly different primary sequences. Of five full-length or near full-length cDNAs representing 17-kDa MBPs, one was missing exons 2 and 5 and four were missing exon 6.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Agrawal H. C., Randle C. L., Agrawal D. In vivo phosphorylation of two myelin basic proteins of developing rabbit brain. J Biol Chem. 1981 Dec 10;256(23):12243–12246. [PubMed] [Google Scholar]
- Amara S. G., Evans R. M., Rosenfeld M. G. Calcitonin/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites. Mol Cell Biol. 1984 Oct;4(10):2151–2160. doi: 10.1128/mcb.4.10.2151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barbarese E., Braun P. E., Carson J. H. Identification of prelarge and presmall basic proteins in mouse myelin and their structural relationship to large and small basic proteins. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3360–3364. doi: 10.1073/pnas.74.8.3360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Battula N., Loeb L. A. The infidelity of avian myeloblastosis virus deoxyribonucleic acid polymerase in polynucleotide replication. J Biol Chem. 1974 Jul 10;249(13):4086–4093. [PubMed] [Google Scholar]
- Breitbart R. E., Nguyen H. T., Medford R. M., Destree A. T., Mahdavi V., Nadal-Ginard B. Intricate combinatorial patterns of exon splicing generate multiple regulated troponin T isoforms from a single gene. Cell. 1985 May;41(1):67–82. doi: 10.1016/0092-8674(85)90062-5. [DOI] [PubMed] [Google Scholar]
- Campagnoni A. T., Campagnoni C. W., Bourre J. M., Jacque C., Baumann N. Cell-free synthesis of myelin basic proteins in normal and dysmyelinating mutant mice. J Neurochem. 1984 Mar;42(3):733–739. doi: 10.1111/j.1471-4159.1984.tb02744.x. [DOI] [PubMed] [Google Scholar]
- Campagnoni C. W., Carey G. D., Campagnoni A. T. Synthesis of myelin basic proteins in the developing mouse brain. Arch Biochem Biophys. 1978 Sep;190(1):118–125. doi: 10.1016/0003-9861(78)90258-8. [DOI] [PubMed] [Google Scholar]
- Carnow T. B., Carson J. H., Brostoff S. W., Hogan E. L. Myelin basic protein gene expression in quaking, jimpy, and myelin synthesis-deficient mice. Dev Biol. 1984 Nov;106(1):38–44. doi: 10.1016/0012-1606(84)90058-7. [DOI] [PubMed] [Google Scholar]
- Carson J. H., Nielson M. L., Barbarese E. Developmental regulation of myelin basic protein expression in mouse brain. Dev Biol. 1983 Apr;96(2):485–492. doi: 10.1016/0012-1606(83)90185-9. [DOI] [PubMed] [Google Scholar]
- Deibler G. E., Krutzsch H. C., Kies M. W. A new form of myelin basic protein found in human brain. J Neurochem. 1986 Oct;47(4):1219–1225. doi: 10.1111/j.1471-4159.1986.tb00743.x. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Greenfield S., Weise M. J., Gantt G., Hogan E. L., Brostoff S. W. Basic proteins of rodent peripheral nerve myelin: immunochemical identification of the 21.5K, 18.5K, 17K, 14K, and P2 proteins. J Neurochem. 1982 Nov;39(5):1278–1282. doi: 10.1111/j.1471-4159.1982.tb12566.x. [DOI] [PubMed] [Google Scholar]
- Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
- Kamholz J., de Ferra F., Puckett C., Lazzarini R. Identification of three forms of human myelin basic protein by cDNA cloning. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4962–4966. doi: 10.1073/pnas.83.13.4962. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kerlero De Rosbo N., Carnegie P. R., Bernard C. C., Linthicum D. S. Detection of various forms of brain myelin basic protein in vertebrates by electroimmunoblotting. Neurochem Res. 1984 Oct;9(10):1359–1369. doi: 10.1007/BF00964663. [DOI] [PubMed] [Google Scholar]
- King C. R., Piatigorsky J. Alternative RNA splicing of the murine alpha A-crystallin gene: protein-coding information within an intron. Cell. 1983 Mar;32(3):707–712. doi: 10.1016/0092-8674(83)90056-9. [DOI] [PubMed] [Google Scholar]
- Kornblihtt A. R., Umezawa K., Vibe-Pedersen K., Baralle F. E. Primary structure of human fibronectin: differential splicing may generate at least 10 polypeptides from a single gene. EMBO J. 1985 Jul;4(7):1755–1759. doi: 10.1002/j.1460-2075.1985.tb03847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Nawa H., Kotani H., Nakanishi S. Tissue-specific generation of two preprotachykinin mRNAs from one gene by alternative RNA splicing. Nature. 1984 Dec 20;312(5996):729–734. doi: 10.1038/312729a0. [DOI] [PubMed] [Google Scholar]
- Roth H. J., Hunkeler M. J., Campagnoni A. T. Expression of myelin basic protein genes in several dysmyelinating mouse mutants during early postnatal brain development. J Neurochem. 1985 Aug;45(2):572–580. doi: 10.1111/j.1471-4159.1985.tb04025.x. [DOI] [PubMed] [Google Scholar]
- Roth H. J., Kronquist K., Pretorius P. J., Crandall B. F., Campagnoni A. T. Isolation and characterization of a cDNA coding for a novel human 17.3K myelin basic protein (MBP) variant. J Neurosci Res. 1986;16(1):227–238. doi: 10.1002/jnr.490160120. [DOI] [PubMed] [Google Scholar]
- Rozek C. E., Davidson N. Drosophila has one myosin heavy-chain gene with three developmentally regulated transcripts. Cell. 1983 Jan;32(1):23–34. doi: 10.1016/0092-8674(83)90493-2. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sorg B. J., Agrawal D., Agrawal H. C., Campagnoni A. T. Expression of myelin proteolipid protein and basic protein in normal and dysmyelinating mutant mice. J Neurochem. 1986 Feb;46(2):379–387. doi: 10.1111/j.1471-4159.1986.tb12979.x. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Takahashi N., Roach A., Teplow D. B., Prusiner S. B., Hood L. Cloning and characterization of the myelin basic protein gene from mouse: one gene can encode both 14 kd and 18.5 kd MBPs by alternate use of exons. Cell. 1985 Aug;42(1):139–148. doi: 10.1016/s0092-8674(85)80109-4. [DOI] [PubMed] [Google Scholar]
- Yu Y. T., Campagnoni A. T. Vitro synthesis of the four mouse myelin basic proteins: evidence for the lack of a metabolic relationship. J Neurochem. 1982 Dec;39(6):1559–1568. doi: 10.1111/j.1471-4159.1982.tb07988.x. [DOI] [PubMed] [Google Scholar]
- de Ferra F., Engh H., Hudson L., Kamholz J., Puckett C., Molineaux S., Lazzarini R. A. Alternative splicing accounts for the four forms of myelin basic protein. Cell. 1985 Dec;43(3 Pt 2):721–727. doi: 10.1016/0092-8674(85)90245-4. [DOI] [PubMed] [Google Scholar]