Recent high-throughput sequencing technologies have discovered various polymerase II transcribed transcripts. The majority of them are non-protein-coding, understudied, and poorly conserved. Noncoding transcripts are categorized based on their location in the genome and the direction in which they are transcribed; these categories classify a noncoding transcript as either antisense, intergenic, or divergent. The RNAs belonging to divergent classes consist of two transcripts, transcribed in sense and antisense direction, generated from the same promoter or locus. Multiple environmental and genetic cues can determine the regulation of these transcripts. One of the well-known signaling molecules, estrogen, has been shown to play a vital role in the activation and regulation of divergent transcripts by mediating effects through the estrogen receptors. Emerging studies have shown a strong causative effect between estrogen-regulated divergent transcripts and diseases such as cancer. However, few, viz., LncRNA67, CUPID1, and CUPID2, show a causal relationship with estrogen-dependent biology. This mini-review summarizes their role in estrogen-dependent processes that may drive the research to identify novel estrogen-signaling regulators
