MicroRNAs 10a and 10b Regulate the Expression of Human Platelet Glycoprotein Ibα for Normal Megakaryopoiesis.
MicroRNAs 10a and 10b Regulate the Expression of Human Platelet Glycoprotein Ibα for Normal Megakaryopoiesis.
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DOI：
10.3390/ijms17111873
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发表时间：
2016-11-09
影响因子：
5.6
通讯作者：
Peng Y
中科院分区：
文献类型：
--
作者：
Zhang Z;Ran Y;Shaw TS;Peng Y
MicroRNA是一类与靶mRNA的3 ′-非编码区（3′-UTR）结合的非编码小RNA。它们引起靶mRNA的切割或翻译抑制，从而调节基因表达。在此，我们使用三种预测工具在人血小板糖蛋白（GP）1BA基因的3′-UTR中寻找潜在的miRNA靶位点。荧光素酶报告基因测定显示miR-10a和-10b位点是功能性的。当miR-10a或-10b模拟物与含有人GP 1BA基因编码区和3′-UTR序列的DNA构建体沿着转染到表达GP Ibβ/GP IX的细胞中时，我们发现它们抑制GP Ibα在细胞表面的瞬时表达。当将miR-10a或-10b模拟物引入小鼠祖细胞时，在巨核细胞分化后，我们发现GP Ibα mRNA表达显着降低，这表明miRNA诱导的mRNA降解正在发挥作用。因此，我们的研究将GP Ibα确定为miR-10a和-10b的新靶点，这表明在巨核细胞生成的晚期阶段，需要急剧降低miR-10a和-10b的水平以允许人GP Ibα的表达和GP Ib-IX-V复合物的形成。
MicroRNAs are a class of small non-coding RNAs that bind to the three prime untranslated region (3′-UTR) of target mRNAs. They cause a cleavage or an inhibition of the translation of target mRNAs, thus regulating gene expression. Here, we employed three prediction tools to search for potential miRNA target sites in the 3′-UTR of the human platelet glycoprotein (GP) 1BA gene. A luciferase reporter assay shows that miR-10a and -10b sites are functional. When miR-10a or -10b mimics were transfected into the GP Ibβ/GP IX-expressing cells, along with a DNA construct harboring both the coding and 3′-UTR sequences of the human GP1BA gene, we found that they inhibit the transient expression of GP Ibα on the cell surface. When the miR-10a or -10b mimics were introduced into murine progenitor cells, upon megakaryocyte differentiation, we found that GP Ibα mRNA expression was markedly reduced, suggesting that a miRNA-induced mRNA degradation is at work. Thus, our study identifies GP Ibα as a novel target of miR-10a and -10b, suggesting that a drastic reduction in the levels of miR-10a and -10b in the late stage of megakaryopoiesis is required to allow the expression of human GP Ibα and the formation of the GP Ib-IX-V complex.
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影响因子：
2.6
作者：
Poujol, CR;Ware, J;Nurden, P
通讯作者：
Nurden, P
影响因子：
11.8
作者：
Lu, Jun;Guo, Shangqin;Golub, Todd R.
通讯作者：
Golub, Todd R.
金属蛋白酶调节可改善小鼠胚胎干细胞的体外产生有效的血小板。
影响因子：
15.3
作者：
Nishikii, Hidekazu;Eto, Koji;Tamura, Noriko;Hattori, Koichi;Heissig, Beate;Kanaji, Taisuke;Sawaguchi, Akira;Goto, Shinya;Ware, Jerry;Nakauchi, Hiromitsu
通讯作者：
Nakauchi, Hiromitsu
影响因子：
4.8
作者：
HASHIMOTO, Y;WARE, J
通讯作者：
WARE, J
DOI：
10.1016/j.bbrc.2010.06.075
发表时间：
2010-07-30
影响因子：
3.1
作者：
Zhong, Yiming;Sullenbarger, Brent;Lasky, Larry C.
通讯作者：
Lasky, Larry C.