# A ribosome-bound pseudoknot in the HCV coding region stimulates viral growth by tuning viral translation

## TL;DR

A new RNA structure in the hepatitis C virus helps control viral growth by regulating protein translation and possibly switching to RNA replication.

## Contribution

Discovery of a pseudoknot in HCV that regulates translation and may influence viral replication.

## Key findings

- A pseudoknot (pk1) in HCV coding region interacts with host ribosomes and inhibits translation.
- Pk1-like structures are found in related viruses, suggesting a conserved regulatory role.
- The pseudoknot may help the virus transition from translation to RNA replication.

## Abstract

Recent studies have uncovered a number of functional RNA structures in RNA viruses, yet their regulatory roles remain poorly understood. Here, using an unbiased proteomic approach alongside targeted biochemical assays, we investigate a previously uncharacterized functional pseudoknot (pk1) within the hepatitis C virus coding region and show that it stably interacts with host ribosomes, inhibiting translation and potentially acting as a regulator between viral translation and RNA genome replication. Comparative structural analysis identifies pk1-like elements in related RNA viruses, suggesting a conserved regulatory mechanism. This study expands the known functions of pseudoknots in viral coding regions beyond frameshifting, highlights the critical role of RNA structure-mediated regulation within viral open reading frames, and provides insight into the design of viral therapeutics and vaccines.

Wan et al. identified a compact pseudoknot structure (pk1) within the HCV ORF that suppresses the translation of viral proteins. Pk1 interacts with host ribosomes in a structure-specific manner, inhibiting upstream and downstream translation. This may help the virus switch from active translation to replication.