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Identification of the new isoforms of mouse myelin basic protein: the existence of exon 5a
J Aruga1, H Okano, K Mikoshiba
1Institute for Protein Research, Osaka University, Japan.
Abstract:
Myelin basic protein (MBP) is a major constituent in the myelin of the CNS. In mice, five forms of MBPs (14 kDa, two types of 17 kDa, 18.5 kDa, and 21.5 kDa) encoded by separate mRNAs have been identified based on cDNA cloning studies. These mRNAs are considered to be produced by alternative splicing from a single gene composed of seven exons. Here we report the existence of two novel MBP mRNAs encoding 19.7-kDa and 21-kDa MBPs identified by cDNA cloning using the polymerase chain reaction. Both of these MBPs contain a sequence of a previously unidentified exon of 66 nucleotides, which was mapped to be just 5' of exon 5 in the MBP gene. MBP mRNAs containing this novel exon (exon 5a) belong to a minor population in the whole brain and PNS and are somewhat enriched in the spinal cord. Exon 5a encodes a very hydrophobic segment rich in valine residues, which presumably forms a beta-pleated sheet.
Insights
Researchers discovered two new myelin basic protein (MBP) messenger RNAs (mRNAs) in mice. These novel forms, generated by an additional exon (exon 5a), contribute to the complex structure of myelin basic protein.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Myelin basic protein (MBP) is a key component of the central nervous system (CNS) myelin sheath.
- Previous studies identified five MBP forms in mice, arising from alternative splicing of a seven-exon gene.
Purpose of the Study:
- To identify novel messenger RNA (mRNA) variants of myelin basic protein (MBP).
- To characterize the genetic basis and potential structural contribution of newly discovered MBP mRNAs.
Main Methods:
- cDNA cloning using the polymerase chain reaction (PCR).
- Gene mapping to determine the location of novel exons within the MBP gene.
Main Results:
- Two novel MBP mRNAs encoding 19.7-kDa and 21-kDa proteins were identified.
- A previously unknown exon (exon 5a) was discovered, located 5' of exon 5 in the MBP gene.
- These novel mRNAs are a minor population, enriched in the spinal cord, and encode a hydrophobic, valine-rich segment.
Conclusions:
- The MBP gene generates additional mRNA diversity through alternative splicing, including the novel exon 5a.
- The newly identified MBP variants contribute to the structural complexity of myelin.
- Exon 5a's encoded hydrophobic segment may play a role in myelin structure or function.