van Oers C C, Adema G J, Zandberg H, Moen T C, Baas P D
Institute of Molecular Biology and Medical Biotechnology, Utrecht University, The Netherlands.
Mol Cell Biol. 1994 Feb;14(2):951-60. doi: 10.1128/mcb.14.2.951-960.1994.
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.
降钙素（CT）/降钙素基因相关肽I（CGRP-I）基因（CALC-I基因）的初级转录本存在组织特异性的可变加工。CT mRNA是甲状腺C细胞中产生的主要mRNA，而CT基因相关肽I mRNA是中枢和外周神经系统神经元中的主要产物。CT特异性外显子4被较弱的加工位点包围。在本研究中，我们调查了外显子4序列是否参与外显子4剪接受体位点的组织特异性选择。结果表明，外显子4 5'部分中两个独立的元件，称为A和B，是产生CT特异性RNA所必需的。这些序列相对于外显子4的5'端位于核苷酸67至88（A）和核苷酸117至146（B）之间。这些序列元件与外显子4的3'剪接位点之间距离的变化不会改变加工选择。这些序列元件在功能上是等效的。CT特异性剪接需要序列A和B同时存在，或者外显子4中任一序列元件的重复。这些序列对RNA加工选择的影响会因CT特异性尿苷分支接受体核苷酸突变为常见的优先腺苷残基而被推翻。
