Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):15952-7. doi: 10.1073/pnas.1414678111. Epub 2014 Oct 27.

Functional conservation despite structural divergence in ligand-responsive RNA switches.

Author information

1
Department of Chemistry and Biochemistry.
2
Division of Infectious Diseases, Department of Medicine, and.
3
Department of Chemistry and Biochemistry, Center for Drug Discovery Innovation, University of California, San Diego, La Jolla, CA 92093 tch@ucsd.edu.

Abstract

An internal ribosome entry site (IRES) initiates protein synthesis in RNA viruses, including the hepatitis C virus (HCV). We have discovered ligand-responsive conformational switches in viral IRES elements. Modular RNA motifs of greatly distinct sequence and local secondary structure have been found to serve as functionally conserved switches involved in viral IRES-driven translation and may be captured by identical cognate ligands. The RNA motifs described here constitute a new paradigm for ligand-captured switches that differ from metabolite-sensing riboswitches with regard to their small size, as well as the intrinsic stability and structural definition of the constitutive conformational states. These viral RNA modules represent the simplest form of ligand-responsive mechanical switches in nucleic acids.

KEYWORDS:

IRES elements; RNA viruses; hepatitis C virus; translation regulation

PMID:
25349403
PMCID:
PMC4234586
DOI:
10.1073/pnas.1414678111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center