hnRNP E1 at the crossroads of translational regulation of epithelial-mesenchymal transition

Abstract

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.

Keywords

Breast cancer / tumor progression / epithelial-mesenchymal transition / cancer stem cells / transforming growth factor-β / translation / hnRNP E1 / PCBP1

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