miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts.
miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts.
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DOI：
10.1016/j.cell.2010.01.007
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发表时间：
2010-03-05
期刊：
影响因子：
64.5
通讯作者：
Perrotti D
中科院分区：
文献类型：
--
作者：
Eiring AM;Harb JG;Neviani P;Garton C;Oaks JJ;Spizzo R;Liu S;Schwind S;Santhanam R;Hickey CJ;Becker H;Chandler JC;Andino R;Cortes J;Hokland P;Huettner CS;Bhatia R;Roy DC;Liebhaber SA;Caligiuri MA;Marcucci G;Garzon R;Croce CM;Calin GA;Perrotti D
microRNA和异质性核糖核蛋白（hnRNP）是以序列特异性方式结合mRNA的转录后基因调节因子。在这里，我们报告了miR-328的丢失发生在急变期慢性髓细胞性白血病（CML-BC）中，通过MAPK-hnRNP E2途径以BCR/ABL剂量和激酶依赖性方式发生。miR-328表达的恢复通过分别与翻译调节剂poly（rC）结合蛋白hnRNP E2和编码存活因子PIM 1的mRNA同时相互作用来挽救白血病母细胞的分化并损害其存活。与hnRNP E2的相互作用不依赖于microRNA的种子序列，并且它导致CEBPA mRNA从hnRNP E2介导的翻译抑制中释放。总之，这些数据揭示了microRNA通过与mRNA靶点的碱基配对和通过干扰调节蛋白功能的诱饵活性来控制细胞命运的双重能力。
MicroRNAs and heterogeneous ribonucleoproteins (hnRNPs) are posttranscriptional gene regulators that bind mRNA in a sequence-specific manner. Here, we report that loss of miR-328 occurs in blast crisis chronic myelogenous leukemia (CML-BC) in a BCR/ABL dose- and kinase-dependent manner through the MAPK-hnRNP E2 pathway. Restoration of miR-328 expression rescues differentiation and impairs survival of leukemic blasts by simultaneously interacting with the translational regulator poly(rC)-binding protein hnRNP E2 and with the mRNA encoding the survival factor PIM1, respectively. The interaction with hnRNP E2 is independent of the microRNA’s seed sequence and it leads to release of CEBPA mRNA from hnRNP E2-mediated translational inhibition. Altogether, these data reveal the dual ability of a microRNA to control cell fate both through base pairing with mRNA targets and through a decoy activity that interferes with the function of regulatory proteins.
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