Long Non-Coding RNA-Mediated Regulation of the Interferon Response: A New Perspective on a Familiar Theme

The interferon (IFN) response is a critical and ubiquitous component of the innate immune response to pathogens. Detailed studies in the last decades have elucidated the function of a large number of proteins that mediate the complex signaling pathways and gene expression programs involved in the interferon response. The recent discovery of the long non-coding RNAs (lncRNAs) as a new category of cellular effectors has led to studies aiming to understand the role of these transcripts in the IFN response. Several high throughput studies have shown that a large number of lncRNAs are differentially expressed following IFN stimulation and/or viral infections. In-depth study of a very small fraction of the identified lncRNAs has revealed critical roles for this class of transcripts in the regulation of multiple steps of the IFN response, and pointed to the presence of an extensive RNA-mediated regulatory network during the antiviral response. As the vast majority of the identified potential regulatory lncRNAs remain unstudied, it is highly likely that future studies will reveal a completely new perspective on the regulation of the IFN response, with lncRNA- and protein-mediated regulatory networks coordinating the duration, magnitude, and character of this aspect of the innate immune response. In addition to providing a more complete picture of the IFN response, these studies will likely identify new therapeutic targets that in the long term may impact the therapeutic options available against microbial infections and diseases of the immune system.