hnRNP E1 at the crossroads of translational regulation of epithelial-mesenchymal transition.
hnRNP E1 at the crossroads of translational regulation of epithelial-mesenchymal transition.
复制标题
DOI：
10.20517/2394-4722.2018.85
复制
发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Howe, Philip H
中科院分区：
文献类型：
--
作者：
Grelet, Simon;Howe, Philip H
上皮-间充质转化（EMT），其中细胞经历从极化的上皮表型到高度能动的成纤维细胞或间充质表型的转换，是胚胎发育期间的基础，并且可以在包括癌症在内的多种疾病中重新激活。时空调节机制不断协调，使细胞在传播到远处器官时能够适应不断变化的环境。虽然许多转录调控因子目前的特点，EMT的转录后控制需要继续调查。hnRNP E1蛋白通过多种非冗余机制调节translatome，在控制肿瘤细胞可塑性中发挥重要作用，当E1缺失时，这种作用得到了例证。hnRNP E1与RNA分子的结合直接或间接地调节特定蛋白质组的翻译：（1）hnRNP E1与特定靶点的结合通过阻止翻译延长而在翻译中起直接作用;（2）hnRNP E1依赖的选择性剪接可以阻止竞争性长非编码RNA的产生，该长非编码RNA充当microRNA（miRNAs）的诱饵。（3）hnRNP E1与转录物3'非翻译区的结合也可以正向调节某些mRNA的稳定性，从而改善其翻译。在全球范围内，hnRNP E1似乎控制蛋白质组重编程在细胞可塑性，无论是通过直接或间接调节蛋白质翻译。
The epithelial-mesenchymal transition (EMT), in which cells undergo a switch from a polarized, epithelial phenotype to a highly motile fibroblastic or mesenchymal phenotype is fundamental during embryonic development and can be reactivated in a variety of diseases including cancer. Spatio-temporally-regulated mechanisms are constantly orchestrated to allow cells to adapt to their constantly changing environments when disseminating to distant organs. Although numerous transcriptional regulatory factors are currently well-characterized, the post-transcriptional control of EMT requires continued investigation. The hnRNP E1 protein displays a major role in the control of tumor cell plasticity by regulating the translatome through multiple non-redundant mechanisms, and this role is exemplified when E1 is absent. hnRNP E1 binding to RNA molecules leads to direct or indirect translational regulation of specific sets of proteins: (1) hnRNP E1 binding to specific targets has a direct role in translation by preventing elongation of translation; (2) hnRNP E1-dependent alternative splicing can prevent the generation of a competing long non-coding RNA that acts as a decoy for microRNAs (miRNAs) involved in translational inhibition of EMT master regulators; (3) hnRNP E1 binding to the 3' untranslated region of transcripts can also positively regulate the stability of certain mRNAs to improve their translation. Globally, hnRNP E1 appears to control proteome reprogramming during cell plasticity, either by direct or indirect regulation of protein translation.