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The PTEN gene is inactivated in various cancers. PTEN has a pseudogene in the human genome, PTENpg1, which up-regulates PTEN expression by acting as a miRNA sponge. Interestingly, one of the antisense RNAs from the PTENpg1 locus, PTENpg1 asRNA α, is found to epigenetically down-regulate PTEN transcription by recruitment of EZH2 and DNMT3a to the PTEN promoter in trans (1). In a recent paper in PNAS, Lister et al. (2) further demonstrate that PTENpg1 asRNA α targeting to the PTEN promoter requires the transcription of the PTEN 5′-UTR region, which is homologous to PTENpg1 asRNA α. This interesting finding contributes to an increase in the knowledge of how noncoding RNAs control gene transcription. The 5′-UTR–containing promoter-spanning transcript is designated as promoter-associated RNA (paRNA). Because paRNA is embedded in the PTEN 5′-UTR, Lister et al. (2) claim that “it is virtually impossible to disentangle to what extent paRNA is either a unique low-copy transcript or the 5′-UTR of the PTEN mRNA.” Indeed, this is …

Transcription start site-associated small RNAs in the PTEN gene