Identification of exon sequences and an exon binding protein involved in alternative RNA splicing of calcitonin/CGRP.

AUTOR(ES)

Cote, G J

RESUMO

Transcripts derived from the 6 exon CALC I gene are differentially processed in a tissue-specific fashion to include or exclude a calcitonin-specific exon 4. All cell types which transcribe a second calcitonin/CGRP gene, CALC II, exclude exon 4. Substitution of the first 30 nucleotides of CALC I exon 4 with analogous CALC II sequence was sufficient to prevent recognition of exon 4 in in vitro or in vivo RNA splicing systems. UV crosslinking detected a approximately 66 kDa RNA-binding protein in HeLa nuclear extract which interacted with CALC I proximal exon sequence, but not CALC II or mutant sequences. UV crosslinking of this protein was inhibited by addition of nuclear extract from a cell type which normally causes exclusion of exon 4. These results identify an important regulatory element within exon 4 and support a model in which calcitonin production requires protein interaction with this sequence to facilitate exon recognition.

Documentos Relacionados

• U1 snRNP-Dependent Function of TIAR in the Regulation of Alternative RNA Processing of the Human Calcitonin/CGRP Pre-mRNA
• Expression of the human calcitonin/CGRP gene in lung and thyroid carcinoma.
• The calcitonin-CGRP gene in the infantile hypercalcaemia/Williams-Beuren syndrome.
• Unusual branch point selection involved in splicing of the alternatively processed Calcitonin/CGRP-I pre-mRNA.
• Sequences involved in the control of adenovirus L1 alternative RNA splicing.