MiR-3120 is a mirror microRNA that targets heat shock cognate protein 70 and auxilin messenger RNAs and regulates clathrin vesicle uncoating.
MiR-3120 is a mirror microRNA that targets heat shock cognate protein 70 and auxilin messenger RNAs and regulates clathrin vesicle uncoating.
复制标题
DOI：
10.1074/jbc.m111.326041
复制
发表时间：
2012-04-27
期刊：
影响因子：
--
通讯作者：
Uney JB
中科院分区：
文献类型：
--
作者：
Scott H;Howarth J;Lee YB;Wong LF;Bantounas I;Phylactou L;Verkade P;Uney JB
背景：已经预测了“镜像”或互补的哺乳动物miRNA，但还没有一个被表征。结果如下：miR-3120和miR-214由相同的内含子基因座产生; miR-3120调节热休克同源蛋白70（Hsc 70）和生长素表达以及囊泡脱壳。结论：miR-3120是一种调节内吞功能的镜像miRNA。镜像miRNAs是重要的哺乳动物基因调控单位，还有更多的miRNAs有待发现和鉴定。我们发现，一个基因位点产生两个完全加工和功能的miRNA，即由于不完美的碱基配对，两个不同的microRNA（miRNA）可以从完全互补的DNA链产生。反义链编码miR-214，其由其自身的启动子转录，而新的miRNA，miR-3120，与其宿主基因mRNA共表达。我们还发现，miR-3120调节细胞功能的重要方面与其宿主基因dynamin-3相似。发现miR-3120位于神经元细胞体中并靶向Hsc 70和生长素，并且其慢病毒介导的表达抑制网格蛋白包被的囊泡的脱壳。最后，镜像miRNAs可能代表了一组新的miRNAs，它们在协调基因表达中具有复杂的作用。
Background: “Mirrored” or complementary mammalian miRNAs have been predicted but none have yet been characterized. Results: miR-3120 and miR-214 are produced from the same intronic locus; miR-3120 regulates heat shock cognate protein 70 (Hsc70) and auxilin expression and vesicle uncoating. Conclusion: miR-3120 is a mirror miRNA regulating endocytic function. Significance: Mirror miRNAs are important mammalian gene regulatory units, and many more remain to be found and characterized. We show that a single gene locus gives rise to two fully processed and functional miRNAs, i.e. that due to imperfect base pairing, two distinct microRNAs (miRNAs) can be produced from the fully complementary DNA strands. The antisense strand encodes miR-214, which is transcribed by its own promoter, whereas a novel miRNA, miR-3120, is co-expressed with its host gene mRNA. We also found that miR-3120 regulates important aspects of cellular function that are similar to that of its host gene, dynamin-3. miR-3120 was found to be located in neuronal cell bodies and to target Hsc70 and auxilin, and its lentivirus-mediated expression inhibited the uncoating of clathrin-coated vesicles. Finally, mirror miRNAs are likely to represent a new group of miRNAs with complex roles in coordinating gene expression.