Structural Studies on the HERV-K Nuclear Export RNA Element

Human endogenous retroviruses (HERVs) are remnants of ancient germline infections that comprise 8% of the human genome. A number of HERVs are actively expressed—their products assume important physiological roles in embryonic development and have been associated with cancer and autoimmune diseases. Expression of a type of HERV, HERV‐K, has been associated with amyotrophic lateral sclerosis (ALS) and some cancers. Expression of the Env protein appears to be dependent on a cis‐acting signal, RcRe, and a viral protein called Rec that mediate nuclear export of unspliced mRNAs in Crm1‐dependent manner, similar to the Rev‐RRE system in HIV. Despite low sequence similarity, the HERV‐K RcRE and HIV RRE are both characterized by a long stem and several smaller stems centered around a junction at the top of the long stem. We recently reported the three‐dimensional structure of the HIV RRE RNA and found that it is a flat, “A”‐shaped molecule (Fang et al., 2013). Based on apparent secondary structure similarities, we hypothesized that the unique “A” shape may be conserved in complex retroviruses. We examined the tertiary structure of the RcRE RNA in solution using small‐angle X‐ray scattering. Our results suggest that the two divergent retroviral elements are structurally conserved, attesting to the significance of the three‐dimensional structure in Rev‐RRE recognition. We report a structure‐ and function‐based mutational analysis of the RcRE tertirary structure. Support or Funding Information Naval Academy Research Council (NARC) DTRA CB Technologies Service Academy Research Initiative. US Naval Academy, Chemistry Department This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .