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Figure 3. Molecular mechanism of hnRNP E1-mediated alternative splicing of PNUTS. A: The PPP1R10 (PNUTS) gene locus can encode either a protein coding mRNA or a non-coding RNA isoform. The PNUTS gene locus is highly conserved between human and mouse and expresses both coding and non-coding transcripts. The lncRNA-PNUTS is generated by the usage of the 3’ alternative splice site (3’ASS) located at the 5’ end of exon 12. This usage leads to the change of the open reading frame and the generation of a premature stop codon; B: the binding of hnRNP E1 to a BAT consensus element located in the alternative splicing site results on its masking and prevents its usage to generate the PPP1R10 mRNA translated into the PNUTS protein; C: loss of hnRNP E1 binding to the alternative splice site uncovers it and allows its usage by the spliceosome machinery. The lncRNA-PNUTS acts as a decoy for miRNA-205 and thus allows the de-repression of ZEB protein translation. Reactivated expression of ZEB proteins induces the shutdown of epithelial markers such as E-Cadherin, allowing EMT to proceed