Rift Valley Fever Virus Nucleocapsid Protein Binds to C/D Box Motifs of snoRNA

Abstract

Rift Valley fever virus (RVFV) is a mosquito‐borne RNA virus that infects livestock and humans. RVFV is widespread in Africa and the Arabian Peninsula, however, no approved vaccines or treatments are available. Nucleocapsid (N) protein in RVFV is RNA binding protein and recognizes its binding target possibly by interacting with a secondary structure or specific sequence of RNA. N protein encapsidates viral RNA in virions to protect its genome. Early in the infection cycle N protein expression is very high, and is more abundant than would be required to interact only with viral RNA. Therefore, it is possible that N protein not only encapsidates its genome but has other functions during infection. In fact we showed, using systematic evolution of ligands by exponential enrichment (SELEX) and cross‐linking, immunoprecipitation and deep sequencing (CLIP‐seq) that N protein is able to bind host RNAs as well as RVFV genomic RNAs. In this study, we investigated characteristics of N protein binding partners. Our data show that N protein preferentially binds to RNAs that contain CUGA/UGA motifs. These motifs are also highly represented in the C and D boxes in small nucleolar RNAs (snoRNAs), whose usual function is to direct 2′‐O‐methylation of specific nucleotides in rRNA. In addition, our CLIP‐seq data, showed that N protein prefers binding to box C/D class snoRNAs over other classes of stable RNAs. Together, these data strongly suggest a non‐canonical function for N protein during RVFV infection that involves binding of small nucleolar RNAs, although the downstream effect of this binding interaction is still incompletely understood and is under investigation.Support or Funding InformationThis project was supported by NIH grants R15AI105737 to JSL and NIGMS P20GM103546 (S. Sprang, PI)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.