Evolution of insulin-like growth factor II: characterization of the mouse IGF-II gene and identification of two pseudo-exons.
Evolution of insulin-like growth factor II: characterization of the mouse IGF-II gene and identification of two pseudo-exons.
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DOI：
10.1089/dna.1990.9.725
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发表时间：
1990-12
影响因子：
3.1
通讯作者：
P. Rotwein;Lisa J. Hall
中科院分区：
文献类型：
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作者：
P. Rotwein;Lisa J. Hall
我们已经克隆了小鼠胰岛素样生长因子II（IGF-II）基因作为一系列重叠粘粒和λ重组体，其特征在于其六个外显子。该基因在小鼠7号染色体上延伸约12 kb，位于胰岛素2基因3'端18 kb处，转录极性相同。外显子1-3编码不同的5'非翻译区，并由三种不同的启动子P1、P2和P3转录成三种IGF-II mRNA，共享共同的编码和3'非翻译序列。启动子P2和P3各自含有TATA盒，并且似乎从单个起始位点指导转录。相比之下，外显子1有三个主要的转录起始位点分布在556个核苷酸，和P1缺乏TATA区域和其他典型的转录控制序列。外显子4-6编码180个氨基酸的IGF-II前体，外显子6还含有3，045个核苷酸的3'非翻译区，其终止于单个多聚腺苷酸化位点。除了6个功能性IGF-II外显子外，我们还鉴定了2个5'“假外显子”，它们似乎是在人类IGF-II中有活性的替代启动子-外显子盒的进化保留的残余物。这种启动子的同源物的损失，指导“成人特异性”表达的IGF-II基因在某些人体组织中，可以解释这种生长因子从大多数小鼠组织中的消失在出生后早期。
We have cloned the mouse insulin-like growth factor II (IGF-II) gene as a series of overlapping cosmid and lambda recombinants and have characterized its six exons. The gene extends over approximately 12 kb of mouse chromosome 7 and is located 18 kb 3' to the insulin 2 gene and in the same transcriptional polarity. Exons 1-3 encode distinct 5' untranslated regions and are transcribed by three different promoters, P1, P2, and P3, into three IGF-II mRNAs sharing common coding and 3' untranslated sequences. Promoters P2 and P3 each contain a TATA box and appear to direct transcription from single initiation sites. By contrast, exon 1 has three major transcriptional start sites distributed over 556 nucleotides, and P1 lacks a TATA region and other typical transcriptional control sequences. Exons 4-6 code for the 180-amino-acid IGF-II precursor, and exon 6 also contains a 3,045-nucleotide 3' untranslated region which ends at a single polyadenylation site. In addition to six functional IGF-II exons, we identified two 5' "pseudo-exons," which appear to be evolutionarily retained remnants of an alternative promoter-exon cassette that is active in human IGF-II. Loss of the homolog of this promoter, which directs "adult-specific" expression of the IGF-II gene in some human tissues, may explain the disappearance of this growth factor from most murine tissues in the early postnatal period.