Organization of the neural cell adhesion molecule (N-CAM) gene: alternative exon usage as the basis for different membrane-associated domains.

Organization of the neural cell adhesion molecule (N-CAM) gene: alternative exon usage as the basis for different membrane-associated domains.
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神经细胞粘附分子 (N-CAM) 基因的组织:替代外显子使用作为不同膜相关结构域的基础。

DOI:
10.1073/pnas.84.1.294
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发表时间:
1987
影响因子:
11.1
通讯作者:
Cunningham,BA
Cunningham,BA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Owens,GC;Edelman,GM;Cunningham,BA

文献摘要

被引文献

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神经细胞粘附分子N-CAM表达为至少三条多肽链(ld、sd和ssd链),其由单个基因指定并在RNA加工期间通过可变剪接和多聚腺苷酸化位点选择而衍生。我们在这里描述了7个重叠的基因组噬菌体克隆与N-CAM cDNA反应的特性,表明鸡N-CAM基因是超过50个酶长。对该基因的分析表明,至少有19个外显子,ld、sd和ssd链的编码序列分别由18、17和15个外显子组装而成。前14个外显子似乎是共同的所有三个链和编码的氨基端部分的N-CAM,其中包含五个串联同源重复类似于那些在免疫球蛋白基因超家族。与包含此类结构域的其他基因相反,N-CAM中的每个片段都由两个外显子指定。每个N-CAM链的羧基末端部分是不同的,这是由于外显子的替代使用。单个外显子编码ssd链的羧基末端26个氨基酸及其mRNA的3'非翻译区,以poly(A)-添加位点结束。两个外显子编码ld和sd链共有的跨膜和胞质序列,另一个外显子编码ld链胞质结构域中发现的另外261个氨基酸。ld和sd链共有的羧基末端21个氨基酸和它们的mRNA共有的3'非翻译区由3475个碱基对的单个大外显子编码,该外显子以第二个poly(A)-添加位点结束。分离编码分子氨基末端和羧基末端区域的外显子的13-腺苷酸酶内含子的序列与身份未知的2-腺苷酸酶poly(A)+ RNA转录物杂交。鸡N-CAM基因的这种描述提供了一个基础,以确定机制,调节N-CAM多肽链在发展过程中的差异表达。
The neural cell adhesion molecule, N-CAM, is expressed as at least three polypeptide chain, (ld, sd, and ssd chains) specified by a single gene and derived by alternative splicing and polyadenylation-site selection during RNA processing. We describe here the characterization of seven overlapping genomic phage clones reactive with N-CAM cDNA, indicating that the chicken N-CAM gene is more than 50 kilobases long. Analysis of the gene shows that there are at least 19 exons and that the coding sequences for the ld, sd, and ssd chains are assembled from 18, 17, and 15 exons, respectively. The first 14 exons appear to be common to all three chains and encode the amino-terminal portion of N-CAM, which contains five tandem homologous repeats resembling those seen in the immunoglobulin gene superfamily. In contrast to other genes containing such domains, each of these segments in N-CAM is specified by two exons. The carboxyl-terminal portion of each N-CAM chain is different as a result of the alternative use of exons. A single exon encodes the carboxyl-terminal 26 amino acids of the ssd chain and the 3' untranslated region of its mRNA, ending with a poly(A)-addition site. Two exons encode the transmembrane and cytoplasmic sequences common to the ld and sd chains, and another exon encodes the additional 261 amino acids found in the cytoplasmic domain of the ld chain. The carboxyl-terminal 21 amino acids common to the ld and sd chains and the 3' untranslated region common to their mRNAs are encoded by a single large exon of 3475 base pairs that ends with a second poly(A)-addition site. Sequences from the 13-kilobase intron that separates the exons encoding the amino-terminal and carboxyl-terminal regions of the molecule hybridize to a 2-kilobase poly(A)+ RNA transcript of unknown identity. This description of the chicken N-CAM gene provides a basis for determining the mechanisms that regulate the differential expression of the N-CAM polypeptide chains during development.