In a letter to the editor, Liu et al. (1) find that PTEN contains some transcript variants that are polyadenylated and prematurely terminated in the first intron of PTEN. These transcripts are suggested to be 5′-UTR–containing promoter-spanning and to encode for three small RNAs (sRNAs), with one of these (sRNA3) being antisense to oligodeoxynucleotide 2 (ODN2), which was one of two ODNs used to interrogate the molecular dynamics and recruitment of DNA methyltransferase 3a to the PTEN promoter (2) (Fig. 1 A and B). Fascinatingly, such endogenous sRNAs could have the capacity to interact with PTEN pseudogene 1-encoded transcripts (Fig. 1C), and consequently act as transcriptional regulators of the PTEN gene, where sRNAs as well as long noncoding RNAs cooperate in regulating endogenous expression of PTEN.