Regulation of alternative pre-mRNA splicing by a novel repeated hexanucleotide element.
The alternatively spliced exon EIIIB is regulated in a cell type-specific manner in the rat fibronectin gene. Splicing of EIIIB into fibronectin mRNA is dependent on sequences in the intron immediately downstream of EIIIB. We show that a short, highly repeated TGCATG motif in this intron is important for cell type-specific recognition of EIIIB as an exon. This motif enhances usage of the EIIIB 5' splice site; furthermore, this repeated TGCATG sequence can activate an alternatively spliced exon in the unrelated rat preprotachykinin pre-mRNA. Interestingly, this sequence can also be found within cis-acting elements identified previously in other alternatively spliced genes. This short repeated TGCATG motif is therefore a cell type-specific element that, in addition to controlling fibronectin alternative splicing, may participate in the regulation of other alternative RNA processing events.
Howard Hughes Medical Institute, Cambridge, Massachusetts.
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D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D015342:DNA Probes; D005091:Exons; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009474:Neurons / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D009928:Organ Specificity; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D015320:Tachykinins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D015342:DNA Probes; D005353:Fibronectins; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin