Microbial Manipulation Host Dark Matter

Abstract

In 2010, Francis Collins, director of the NIH, referenced the transcribed yet untranslated component of the human genome as ‘dark matter’, a term often used by astrophysicists to describe the vast quantities of invisible hypothetical matter known to make up the majority of our universe. Since then, geneticists have set out to shed light on this matter with remarkable success, in an array of biological contexts ranging from cancer to developmental biology. In recent years, rapid advances have been made towards uncovering the functional biological roles of long noncoding RNAs (lncRNAs), which have been estimated to represent 70–90 % of mammalian genomic dark matter. It has become increasingly evident that the primary function of our noncoding genome is to regulate the coding genome. This makes genomic dark matter an attractive evolutionary target for pathogens, who need to alter the cellular host environment in order to promote their survival and propagation. In this review, we focus on the constituents of the mammalian genomic dark matter that are manipulated by viral and microbial pathogens. We also dive deeper into the involvement of ncRNAs, including enhancer RNAs (eRNAs), in the innate immune response against intracellular pathogens. This commentary further highlights how dark and abstruse our noncoding genome still is, particularly in the context of infection biology.