Expression profiling of TGF-beta-induced and hnRNP E1-mediated epithelial-mesenchymal transition

ABSTRACT: Regulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3’-UTR regulatory BAT (TGFβ activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3’-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts. We adopted a combinatorial approach involving polysome profiling and RIP-Chip analyses using hnRNP E1 and filtered the array data based on the regulatory mechanism of Dab2 and ILEI. This led to the identification and validation of a cohort of target mRNAs that follow the same pattern of regulation as Dab2 and ILEI.

ORGANISM(S): Mus musculus

PROVIDER: GSE40466 | GEO | 2012/08/30

SECONDARY ACCESSION(S): PRJNA174133

REPOSITORIES: GEO