2 DIFFERENT SEQUENCE ELEMENTS WITHIN EXON-4 ARE NECESSARY FOR CALCITONIN-SPECIFIC SPLICING OF THE HUMAN CALCITONIN CALCITONIN-GENE-RELATED PEPTIDE-I PRE-MESSENGER-RNA
Ccm. Vanoers et al., 2 DIFFERENT SEQUENCE ELEMENTS WITHIN EXON-4 ARE NECESSARY FOR CALCITONIN-SPECIFIC SPLICING OF THE HUMAN CALCITONIN CALCITONIN-GENE-RELATED PEPTIDE-I PRE-MESSENGER-RNA, Molecular and cellular biology, 14(2), 1994, pp. 951-960
The calcitonin (CT)/calcitonin gene-related peptide I (CGRP-I) gene (C
ALC-I gene) is subject to alternative tissue-specific processing of it
s primary transcript. CT mRNA is the predominant mRNA produced in thyr
oid C tells, whereas CT gene-related peptide I mRNA is the main produc
t in neurons of the central and peripheral nervous systems. The CT-spe
cific exon 4 is surrounded by weak processing sites. In this study we
have investigated whether exon 4 sequences are involved in the tissue-
specific selection of the exon I splice acceptor site. The results ind
icate that two separate elements, termed A and B, in the 5' part of ex
on 4 are required for production of CT-specific RNA. These sequences a
re located between nucleotides 67 and 88 (A) and nucleotides 117 and 1
46 (B) relative to the 5' end of exon 4. Variation of the distance bet
ween these sequence elements and the 3' splice site of exon 4 does not
change the processing choice. These sequence elements are functionall
y equivalent. CT-specific splicing requires the presence of both seque
nce A and B or duplicates of either sequence element in exon 4. The ef
fect of these sequences on the RNA processing choice is overruled by m
utation of the CT-specific uridine branch acceptor nucleotide into a c
ommonly preferred adenosine residue.