DIFFERENTIAL EXON USAGE INVOLVING AN UNUSUAL SPLICING MECHANISM GENERATES AT LEAST 8 TYPES OF NCAM CDNA IN MOUSE-BRAIN
DIFFERENTIAL EXON USAGE INVOLVING AN UNUSUAL SPLICING MECHANISM GENERATES AT LEAST 8 TYPES OF NCAM CDNA IN MOUSE-BRAIN
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DOI：
10.1002/j.1460-2075.1989.tb03389.x
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发表时间：
1989-02-01
期刊：
影响因子：
11.4
通讯作者：
WILLE, W
中科院分区：
文献类型：
--
作者：
SANTONI, MJ;BARTHELS, D;WILLE, W
已知小鼠神经细胞粘附分子 (NCAM) 以三种不同大小的亚型存在，即 NCAM-180、-140 和 -120，由长度为 6,9、6.1、4.8 和 2.7 kb 的四个转录本编码。由于这些亚型之间的差异是由于跨膜和细胞质结构域的编码区中的选择性剪接造成的，因此 NCAM 的胞外 N 端部分似乎是所有三种蛋白质形式所共有的。在这里，我们报道NCAM的N端结构域的编码区还包含至少两个可变剪接位点，称为a和.pi。可以在这些位点处引入长度为3,18和30nt的短附加序列，它们分别位于Ig样结构域和膜附着位点之间的近膜“茎”中以及Ig样结构域IV内。通过对选定的独立 cDNA 克隆进行测序和 S1 核酸酶保护测定以及 Northern 印迹分析，已经发现了至少八种不同 mRNA 的证据。如果迄今为止在小鼠大脑中发现的大多数剪接模式组合都发生了，则可以生成编码 18 种不同蛋白质的 24 种不同的 mRNA。在剪接位点 a 插入的最短额外序列仅由三核苷酸 AAG 组成，这引发了关于这种特定插入机制的疑问。
The murine neural cell adhesion molecule (NCAM) is known to exist in three isoforms of different size, NCAM-180, -140 and -120 coded for by four transcripts of 6,9, 6.1, 4.8 and 2.7 kb in length. Since the differences between these isoforms are due to alternative splicing in the coding region for the transmembrane and cytoplasmic domains, the extracellular, N-terminal portion of NCAM seemd to be shared by all three protein forms. Here we report that the coding region for N-terminal domains of NCAM also contains at least two sites of alternative splicing, termed a and .pi.. Short additonal sequences of 3,18 and 30 nt in length can be introduced at these sites, which are located in the membrane-proximal ''stem'' between the Ig-like domains and the membrane attachment site and within the Ig-like domain IV, respectively. Proof for at least eight different mRNAs has been found by sequencing and S1 nuclease protection assays of selected independent cDNA clones, and Northern blot analyses. If most combination of the splice patterns identified so far in mouse brain occurred, 24 different mRNAs could be generated coding for 18 different proteins. The shortest extra-sequence found inserted at splice site a consisted only of the trrinucleotide AAG, raising questions about the mechanism of this particular insertion.