2 INDEPENDENT AND INTERACTIVE DNA-BINDING SUBDOMAINS OF THE PAX6 PAIRED DOMAIN ARE REGULATED BY ALTERNATIVE SPLICING
2 INDEPENDENT AND INTERACTIVE DNA-BINDING SUBDOMAINS OF THE PAX6 PAIRED DOMAIN ARE REGULATED BY ALTERNATIVE SPLICING
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DOI：
10.1101/gad.8.17.2022
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发表时间：
1994-09-01
影响因子：
10.5
通讯作者：
MAAS, RL
中科院分区：
文献类型：
--
作者：
EPSTEIN, JA;GLASER, T;MAAS, RL
脊椎动物Pax蛋白共有一个保守的128个氨基酸的DNA结合基序，配对结构域。PAX 6基因在小鼠小眼和人类无虹膜发育缺陷中突变，也编码在配对结构域中具有14个氨基酸插入的第二种蛋白质。这种蛋白质由mRNA选择性剪接产生，具有独特的DNA结合特性。与其他主要通过氨基末端结合DNA的配对结构域不同，扩展的Pax 6配对结构域仅通过其羧基末端与DNA相互作用。这种性质可以通过从Pax 6或Pax 2配对结构域中缺失30个氨基末端残基来模拟。因此，插入作为一种分子切换，以揭露羧基末端的DNA结合潜力。两种Pax 6蛋白的功能不等价性通过在选择性剪接受体位点的位置-3处的T -> C突变来强调，该突变改变两种同种型的比率并引起不同的人类眼部综合征。
Vertebrate Pax proteins share a conserved 128-amino-acid DNA-binding motif, the paired domain. The PAX6 gene, which is mutated in the murine Small eye and human aniridia developmental defects, also encodes a second protein with a 14-amino-acid insertion in the paired domain. This protein, which arises by alternative mRNA splicing, exhibits unique DNA-binding properties. Unlike other paired domains, which bind DNA predominantly by their amino termini, the extended Pax6 paired domain interacts with DNA exclusively through its carboxyl terminus. This property can be simulated by deletion of 30 amino-terminal residues from the Pax6 or Pax2 paired domains. Thus, the insertion acts as a molecular toggle to unmask the DNA-binding potential of the carboxyl terminus. The functional nonequivalence of the two Pax6 proteins is underscored by a T --> C mutation at position -3 of the alternative splice acceptor site that changes the ratio of the two isoforms and causes a distinct human ocular syndrome.