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PMID: 8289835 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Two different sequence elements within exon 4 are necessary for calcitonin-specific splicing of the human calcitonin/calcitonin gene-related peptide I pre-mRNA.

Molecular and cellular biology ·Vol. 14 ·No. 2 ·1994-02-00 ·Pages 951-60

van Oers CC, Adema GJ, Zandberg H, Moen TC, Baas PD

Abstract

The calcitonin (CT)/calcitonin gene-related peptide I (CGRP-I) gene (CALC-I gene) is subject to alternative tissue-specific processing of its primary transcript. CT mRNA is the predominant mRNA produced in thyroid C cells, whereas CT gene-related peptide I mRNA is the main product in neurons of the central and peripheral nervous systems. The CT-specific 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 4 splice acceptor site. The results indicate that two separate elements, termed A and B, in the 5' part of exon 4 are required for production of CT-specific RNA. These sequences are located between nucleotides 67 and 88 (A) and nucleotides 117 and 146 (B) relative to the 5' end of exon 4. Variation of the distance between these sequence elements and the 3' splice site of exon 4 does not change the processing choice. These sequence elements are functionally equivalent. CT-specific splicing requires the presence of both sequence A and B or duplicates of either sequence element in exon 4. The effect of these sequences on the RNA processing choice is overruled by mutation of the CT-specific uridine branch acceptor nucleotide into a commonly preferred adenosine residue.

Related Genes
CALC-I CGRP-I
MeSH Terms
Alternative Splicing Base Sequence Calcitonin/biosynthesis,genetics Calcitonin Gene-Related Peptide/genetics Cell Line DNA Primers Exons Humans Molecular Sequence Data Polymerase Chain Reaction RNA Precursors/metabolism RNA Processing, Post-Transcriptional RNA, Messenger/biosynthesis,metabolism Regulatory Sequences, Nucleic Acid Restriction Mapping Sequence Deletion Transcription, Genetic Transfection
Chemicals
DNA Primers RNA Precursors RNA, Messenger Calcitonin Calcitonin Gene-Related Peptide
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
van Oers C C
Institute of Molecular Biology and Medical Biotechnology, Utrecht University, The Netherlands.
Adema G J
Zandberg H
Moen T C
Baas P D
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.2.951-960.1994
Published
1994-02-00
Pages
951-60
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358450
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.14.2.951-960.1994 PMC Full Text View journal details
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