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Gene structure of mammalian acetylcholinesterase. Alternative exons dictate tissue-specific expression
- Source :
- Journal of Biological Chemistry. 266:23083-23090
- Publication Year :
- 1991
- Publisher :
- Elsevier BV, 1991.
-
Abstract
- The genes encoding mouse and human acetylcholinesterases have been cloned from genomic and cosmid libraries. Restriction analysis and a comparison of sequence with the cDNAs have defined the exon-intron boundaries. In mammals, three invariant exons encode the signal peptide and the amino-terminal 535 amino acids common to all forms of the enzyme whereas alternative exon usage of the next exon accounts for the structural divergence in the carboxyl termini of the catalytic subunits. mRNA protection studies show that the cDNA encoding the hydrophilic catalytic subunits represents the dominant mRNA species in mammalian brain and muscle whereas divergent mRNA species are evident in cells of hematopoietic origin (bone marrow cells and a erythroleukemia cell line). Analyses of mRNA species in these cells and the genomic sequence have enabled us to define two alternative exons in addition to the one found in the cDNAs; they encode unique carboxyl-terminal sequences. One mRNA consists of a direct extension through the intervening sequence between the common exon and the 3' exon deduced from the cDNA. This sequence encodes a subunit lacking the cysteine critical to oligomer formation. Another mRNA results from a splice that encodes a stretch of hydrophobic amino acids immediately upstream of a stop codon. This exon, when spliced to the upstream invariant exons, should encode glycophospholipid-linked species of the enzyme. Homologous sequence, identity of exon-intron junctions, and identity of position of the stop codon are seen for this region in mouse and human. Polymerase chain reactions carried out across the expected intron region and mRNA protection studies show that this splice occurs in mouse bone marrow and erythroleukemia cells yielding the appropriate cDNA.
- Subjects :
- RNA Splicing
Molecular Sequence Data
Restriction Mapping
Biology
Exon shuffling
Polymerase Chain Reaction
Biochemistry
Mice
Exon
Ribonucleases
Exon trapping
Sequence Homology, Nucleic Acid
Tumor Cells, Cultured
Animals
Humans
Amino Acid Sequence
Molecular Biology
Gene
Mammals
Splice site mutation
Base Sequence
Intron
DNA
Exons
Cell Biology
Blotting, Northern
Molecular biology
Introns
Stop codon
Organ Specificity
Acetylcholinesterase
Tandem exon duplication
Sequence Alignment
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 266
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....50b8bfe82a1ffd6b493d554aa6fcea84