The “Topological Train Ride” of a viral long non-coding RNA

Abstract

As the notion of small molecule targeting of regulatory viral and cellular RNAs gathers momentum, understanding their structure, and variations thereof, in the appropriate biological context will play a critical role. This is especially true of the ∼1100-nt polyadenylated nuclear (PAN) long non-coding (lnc) RNA of Kaposi's sarcoma herpesvirus (KSHV), whose interaction with viral and cellular proteins is central to lytic infection. Nuclear accumulation of PAN RNA is mediated via a unique triple helical structure at its 3′ terminus (within the expression and nuclear retention element, or ENE) which protects it from deadenylation-dependent decay. Additionally, significant levels of PAN RNA have been reported in both the cytoplasm of KSHV-infected cells and in budding virions, leading us to consider which viral and host proteins might associate with, or dissociate from, this lncRNA during its “journey” through the cell. By combining the power of SHAPE-mutational profiling (SHAPE-MaP) with large scale virus culture facilities of the National Cancer Institute, Frederick MD, Sztuba-Solinska et al. have provide the first detailed description of KSHV PAN nucleoprotein complexes in multiple biological contexts, complementing this by mapping sites of recombinant KSHV proteins on an in vitro-synthesized, polyadenylated counterpart.