Alternate Pax7 paired box transcripts which include a trinucleotide or a hexanucleotide are generated by use of alternate 3' intronic splice sites which are not utilized in the ancestral homologue.
In the mouse, Pax7 plays an important role in development of the skeletal muscles of the limbs, elements of the nervous system and cranio-facial structures. It is expressed in the brain and skeletal muscles of the limbs in the mature mouse. Recently, we have identified alternate transcripts that differ by inclusion or exclusion of a trinucleotide and/or a hexanucleotide in the paired domain encoding region. Sequencing of the paired box in genomic DNA from SJL/J and BALB/c mice reveals that the trinucleotide and hexanucleotide are generated by selection of alternate splice sites at the 3' terminus of each of the two paired box introns, respectively. The proximal 3' splice site of the first intron, which includes the trinucleotide in the mature transcript, is preferentially selected in skeletal muscle and brain. By contrast, the proximal 3' splice site of the second intron, which results in inclusion of the hexanucleotide in the mature transcript, is preferentially selected only in skeletal muscle. The distal alternate 3' splice site, which results in exclusion of the hexanucleotide in the mature transcript, is preferentially selected in the brain. These findings raise the possibility that there may be tissue-specific factors that influence the specificity of the spliceosomal machinary. Reference to the structure of the proposed primordial form of Pax7 suggests that the ability to utilize the alternate splice sites that generate inclusion of the trinucleotide and the hexanucleotide in the mature transcripts may have occurred in recent evolutionary times.
Kay
P H
PH
Molecular Pathology Laboratory, Department of Pathology, The University of Western Australia, Nedlands, Western Australia 6907, Australia.
Ziman
M R
MR
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D018398:Homeodomain Proteins; D007438:Introns / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009843:Oligoribonucleotides / Q000235:genetics; D051763:PAX7 Transcription Factor; D017381:Spliceosomes / Q000235:genetics; D014158:Transcription, Genetic
D018398:Homeodomain Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D009843:Oligoribonucleotides; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse