Fig. 3

Regulation of PTEN by the sense and antisense transcripts of its processed pseudogene PTENP1: regulating the regulator of PI3K signalling. PTENP1 is transcribed into a sense and 2 antisense transcripts (a and b). In the cytoplasm, the sense transcript (PTENP1(S)) acts as competing endogenous RNA, competing with PTEN for the binding of PTEN-targeting miRNAs and thus freeing PTEN from miRNA-mediated repression and increasing PTEN cellular abundance. Of the 2 antisense PTENP1 transcripts, PTENP1(AS)α and PTENP1(AS)β produced, PTENP1(AS)α acts in the nucleus to negatively regulate PTEN transcription by recruiting chromatin-repressor proteins, the Enhancer of Zeste Homolog 2 and DNA methyltransferase 3a (EZH2) and DNA methyltransferase 3a (DNMT3a) to the PTEN promoter. Conversely, also in the cytoplasm, PTENP1(AS)β acts to stabilise the PTENP1(S) transcript through RNA-RNA interactions, as this the sense transcript lacks a poly(A) tail, and hence reinforces the miRNA ‘sponging’ activity of PTENP1(S) (modified from [42])