Viral RNA genomes are widely recognized to be intricately structured, containing motifs that are conserved across multiple strains. These motifs are crucial for viral genome recognition by viral and host proteins and consequently for functions such as replication and translation. The hepatitis C virus (HCV) genome contains a 46-nucleotide stem-loop structured RNA motif, 5BSL3.2, which is a part of the network of integral RNA-RNA interactions in the genome. The motif has critical regulatory functions as it also mediates RNA-protein interactions with the HCV RNA-dependent RNA polymerase, NS5B, thereby controlling replication and translation. Both 5BSL3.2 and NS5B have been reported to possess a binding site for hnRNP A1, an abundant host protein that regulates numerous cellular processes. The molecular mechanism of the interactions between the motif and each of the proteins as well as between the two proteins is not well understood. In this work, we have identified and characterized the sequence and structural motifs of 5BSL3.2 that are crucial for binding NS5B and hnRNP A1. We discuss the interplay between the RNA motif and the proteins, and elucidate how these proteins distinctly interact with the motif. This work lays the foundation for understanding how viral genomes hijack host modalities to promote viral replication.
Gupte et al. (Sun,) studied this question.