The Viral and Eukaryotic Distribution of the Internal Ribosome Entry Site (IRES) and its Potential as an Anti-Viral Translation Target
Abstract
Picornaviruses and flaviviruses are responsible for an enormous variety of medically important human and animal diseases which include the common cold (rhinoviruses), poliomyelitis (poliovirus), and hepatitis C. The majority of mRNAs initiate translation by the binding of ribosomes to the 5' cap structure, followed by ribosomal scanning of the mRNA until the appropriate AUG start codon is encountered. In contrast, translation of the mRNA of naturally uncapped picornaviruses and some flaviviruses, notably hepatitis Cand pestivirus, is mediated by a mechanism involving internal initiation of translation. The sequence responsible for cap-independent, internal ribosome binding is within the 5'untranslated region (UTR) of the mRNA and forms a complex secondary structure, termed the internal ribosome entry site (IRES). This mechanism of internal initiation, once thought to be unique to viruses, is utilized by several eukaryotic mRNAs such as the ones encoding heavy chain immunoglobulin binding protein, BiP, Drosophila Antp protein, c-myc, and eIF4G. The serendipitous discovery of an IRES inhibitory RNA a-RNA) in Saccharomyces cerevisiae has laid a solid foundation for investigating anti-IRES agents as anti-viral agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 16, 1998
- Accession Number
- AD1011774
Entities
People
- Alicia T. Crowder
Organizations
- Uniformed Services University of the Health Sciences