Noncoding RNA-guided recruitment of transcription factors: A prevalent but undocumented mechanism?

High-fidelity binding of transcription factors (TFs) to DNA target sites is fundamental for proper regulation of cellular processes, as well as for the maintenance of cell identity. Recognition of cognate binding motifs in the genome is attributed by and large to the DNA binding domains of TFs. As an additional mode of conferring binding specificity, noncoding RNAs (ncRNAs) have been proposed to assist associated TFs in finding their binding sites by interacting with either DNA or RNA in the vicinity of their target loci. However, a well-documented example of such a mechanism was lacking until we recently reported that a ncRNA made by Epstein-Barr virus uses an RNA-RNA interaction with nascent transcripts generated from the viral genome to facilitate the recruitment of an interacting TF, PAX5, to viral DNA. This proof-of-principle finding suggests that cellular ncRNAs may likewise function in guiding interacting TFs to chromatin target sites.