Abstract

It is becoming increasingly clear that noncoding RNAs (ncRNAs) may constitute a new layer of regulatory control over gene expression programs in many organisms. ncRNAs are loosely grouped into two major classes based on their size: small ncRNAs less than 200 nt, and long ncRNAs (lncRNAs). LncRNAs have been shown to regulate gene expression by deploying epigenetic modification and modulating transcription, mRNA splicing, and translation, during which they may function as guides, decoys, or scaffolds for gene regulating proteins. Although these models predict most of the known lncRNA functions, the detailed mechanisms are poorly elucidated. In our recent study we identified a cytoplasmic lncRNA called NFκB interacting long noncoding RNA (NKILA) that interacts with NFκB and represses IκB phosphorylation by physically hindering the phosphorylation site of IκB. NKILA is transcriptionally activated by NFκB signaling upon challenge by proinflammatory cytokines, and forms a negative feedback loop for NFκB regulation. NKILA differs from other known NFκB negative feedback loops in that it acts at the level of IκB phosphorylation, which constitutes a physiological barrier to prevent NFκB over activation under conditions of persistently elevated IKK . As a “gate keeper” for aberrant NFκB activation, NKILA is subjected to microRNA-mediated degradation and its expression is decreased in various types of cancer including breast, liver, lung, and colon cancers. Reduced NKILA expression in advanced cancers may result in NFκB over activation and the consequential cancer metastasis. Our findings have revealed a new class of lncRNAs that directly interact with proteins involved in signal transduction pathways and interfere with cell signaling. This implicates a potential strategy for the design of RNA -based targeted drugs.