ID: 259: Innate immune non-coding and coding RNA networks regulated by interferon

Abstract

The innate immune response is a finely tuned reaction of balanced positive and negative signals that ensure the response is appropriate to defend the host – induction of appropriate effector molecules, short duration, and appropriate strength. An imbalanced response can lead to acute and chronic inflammatory diseases. A relatively new level of control of signaling in biological processes occurs via non-coding (Nnc) RNA, including microRNA (miR) and long non-coding RNA (lnc RNA), which modulate the translation of effector gene transcripts. We have developed a resource (Interferome.org) that documents and functionally annotates the transcripts induced and repressed after treatment with interferon (IFN), a key cytokine that regulates innate immunity. We now report data generated from an RNA Seq analysis of a time-course of macrophage response to IFN□. We have analysed the data by standard protocols and proprietary tools (RNA eXpress; S. Forster et al., Bioinformatics 2013 15;29:810–2) to facilitate the identification of novel transcripts. The results show a new level of appreciation of the extent of up- and down-regulation of hundreds of miRs and other ncRNA by IFN as well as ‘editing’ of coding transcripts. We have performed HITS-CLIP to immunoprecipitate miRs bound to their target coding transcripts, thus identifying about 3800 transcripts were targeted by >100 IFN regulated miR 3 h post induction. This data represent a wealth of information on the regulatory networks of ncRNA that are operational during an IFN response and could be the basis of future diagnostics or targets for regulating the innate immune response.