miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1.
miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1.
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DOI：
10.4161/rna.1.2.1066
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发表时间：
2004-07-01
期刊：
影响因子：
4.1
通讯作者：
Taylor, John M
中科院分区：
文献类型：
--
作者：
Chang, Jinhong;Nicolas, Emmanuelle;Taylor, John M
这些研究表明，miR-122，一个22个核苷酸的microRNA，来源于肝脏特异性的非编码多腺苷化RNA，转录自hcr基因。从哺乳动物到鱼类，miR-122的确切序列以及hcr mRNA内邻近的二级结构都是保守的。小鼠肝脏中的miR-122水平在胚胎发生的第17天左右增加到最大值的一半，并且在出生前达到每个平均细胞50,000拷贝的最高水平。Lewis等人（2003）预测阳离子氨基酸转运蛋白（CAT-1或SLC7A1）是miR-122的靶标。CAT-1蛋白及其mRNA在所有哺乳动物组织中均有表达，但在成人肝脏中表达水平较低。此外，在小鼠肝脏发育过程中，CAT-1 mRNA与miR-122几乎呈负相关下降。在人类CAT-1 mRNA中预测了8个潜在的miR-122靶点，其中6个位于3'-未翻译区。使用报告基因构建，研究人员发现，只有三个预测位点，连接在人类CAT-1的400个核苷酸序列中，具有协同作用，足以强烈抑制蛋白质合成并降低mRNA水平。总之，这些研究追踪了miR-122在其mRNA前体hcr发育过程中的积累，直到鉴定可能是特定mRNA靶点CAT-1。
These studies show that miR-122, a 22-nucleotide microRNA, is derived from a liver-specific noncoding polyadenylated RNA transcribed from the gene hcr. The exact sequence of miR-122 as well as the adjacent secondary structure within the hcr mRNA are conserved from mammalian species back to fish. Levels of miR-122 in the mouse liver increase to half maximal values around day 17 of embryogenesis, and reach near maximal levels of 50,000 copies per average cell before birth. Lewis et al. (2003) predicted the cationic amino acid transporter (CAT-1 or SLC7A1) as a miR-122 target. CAT-1 protein and its mRNA are expressed in all mammalian tissues but with lower levels in adult liver. Furthermore, during mouse liver development CAT-1 mRNA decreases in an almost inverse correlation with miR-122. Eight potential miR-122 target sites were predicted within the human CAT-1 mRNA, with six in the 3'-untranslated region. Using a reporter construct it was found that just three of the predicted sites, linked in a 400-nucleotide sequence from human CAT-1, acted with synergy and were sufficient to strongly inhibit protein synthesis and reduce mRNA levels. In summary, these studies followed the accumulation during development of miR-122 from its mRNA precursor, hcr, through to identification of what may be a specific mRNA target, CAT-1.