Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites
Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites
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DOI：
10.1016/s0012-1606(03)00126-x
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发表时间：
2003-06-15
影响因子：
2.7
通讯作者：
Tang, LJ
中科院分区：
文献类型：
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作者：
Moss, EG;Tang, LJ
异时基因lin-28是秀丽隐杆线虫发育时间的调节因子。它必须在第一个幼虫阶段表达，并在第二个阶段下调以正常发育。这种下调部分由lin-4（一种21-nt的微小RNA）介导。如果下调由于lin-28 3' UTR中与lin-4互补的短序列突变而失败，则多种体细胞谱系在发育中不能正常进展。在这里，我们报告说，林-28同源物存在于不同的动物，包括果蝇，爪蟾，小鼠和人类。这些同源物的特征在于LIN-28蛋白的RNA结合基序的不寻常配对：冷休克结构域（CSD）和一对逆转录病毒型CCHC锌关节。LIN-28蛋白的保守性表明它们不同于动物的其他保守的含CSD蛋白家族，即Y盒蛋白。重要的是，果蝇，非洲爪蟾和小鼠的LIN-28蛋白似乎在发育过程中表达和下调，与这种发育时序调节剂的保守作用一致。此外，小鼠和人Lin-28基因的极长3'UTR显示出广泛的序列同一性区域，其包含与秀丽隐杆线虫lin-4和let-7 microRNA的哺乳动物同源物互补的位点，表明microRNA调控是不同动物中Lin-28基因的保守特征。(C)2003 Elsevier Science（美国）。All rights reserved.
The heterochronic gene lin-28 is a regulator of developmental timing in the nematode Caenorhabditis elegans. It must be expressed in the first larval stage and downregulated by the second stage for normal development. This downregulation is mediated in part by lin-4, a 21-nt microRNA. If downregulation fails due to a mutation in a short sequence in the lin-28 3' UTR that is complementary to lin-4, then a variety of somatic cell lineages fail to progress normally in development. Here, we report that Lin-28 homologues exist in diverse animals, including Drosophila, Xenopus, mouse, and human. These homologues are characterized by the LIN-28 protein's unusual pairing of RNA-binding motifs: a cold shock domain (CSD) and a pair of retroviral-type CCHC zinc knuckles. Conservation of LIN-28 proteins shows them to be distinct from the other conserved family of CSD-containing proteins of animals, the Y-box proteins. Importantly, the LIN-28 proteins of Drosophila, Xenopus, and mouse each appear to be expressed and downregulated during development, consistent with a conserved role for this regulator of developmental timing. In addition, the extremely long 3' UTRs of mouse and human Lin-28 genes show extensive regions of sequence identity that contain sites complementary to the mammalian homologues of C elegans lin-4 and let-7 microRNAs, suggesting that microRNA regulation is a conserved feature of the Lin-28 gene in diverse animals. (C) 2003 Elsevier Science (USA). All rights reserved.