A New Mechanism of Gene Regulation Mediated by Noncoding RNA

Cytokines play a critical role in innate and adaptive immunity, acting as messenger molecules that regulate the growth, survival, and function of cells. The revolution in recombinant DNA techniques in the late 1970s led to the molecular cloning of cDNAs encoding a number of cytokines. By the mid-1980s, many of these had been identified and were revealed to be relatively small secreted proteins with diverse primary structures. The pleiotropic actions of cytokines, which underpin the complex interaction between the immune system and other tissues, were only beginning to be appreciated. With the identification of their gene sequences, it was possible to examine how the expression of cytokines was regulated at the molecular level. It was widely appreciated that answering this question would give insights into how the immune response was coordinated and how altered regulation of cytokines might contribute to disease. The factors controlling gene expression at the molecular level were only starting to be understood (e.g.,theidentification of promotersandenhancers that regulate gene transcription in tissue-specific and inducible manners). However, the mechanisms by which these factors functioned remained poorly defined. Accordingly, the publication of the paper we highlight in this commentary coincided with the discovery of NF-kB and predated the identification of NFAT and STAT transcription factors, which are among the most often encountered regulators of cytokine gene transcription.