Open AccessTargeting internal ribosome entry site (IRES)‐mediated translation to block hepatitis C and other RNA viruses
Author(s) -
Dasgupta Asim,
Das Saumitra,
Izumi Raquel,
Venkatesan Arun,
Barat Bhaswati
Publication year - 2004
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.2004.tb09533.x
Subject(s) - internal ribosome entry site , translation (biology) , five prime untranslated region , initiation factor , eukaryotic translation , biology , rna , virology , untranslated region , protein biosynthesis , eukaryotic initiation factor , ribosome , microbiology and biotechnology , messenger rna , genetics , gene
A number of RNA‐containing viruses such as hepatitis C (HCV) and poliovirus (PV) that infect human beings and cause serious diseases use a common mechanism for synthesis of viral proteins, termed internal ribosome entry site (IRES)‐mediated translation. This mode of translation initiation involves entry of 40S ribosome internally to the 5′ untranslated region (UTR) of viral RNA. Cap‐dependent translation of cellular mRNAs, on the other hand, requires recognition of mRNA 5′ cap by the translation machinery. In this review, we discuss two inhibitors that specifically inhibit viral IRES‐mediated translation without interfering with cellular cap‐dependent translation. We present evidence, which suggest that one of these inhibitors, a small RNA (called IRNA) originally isolated from the yeast Saccharomyces cerevisiae , inhibits viral IRES‐mediated translation by sequestering both noncanonical transacting factors and canonical initiation factors required for IRES‐mediated translation. The other inhibitor, a small peptide from the lupus autoantigen La (called LAP), appears to block binding of cellular transacting factors to viral IRES elements. These results suggest that it might be possible to target viral IRES‐mediated translation for future development of therapeutic agents effective against a number of RNA viruses including HCV that exclusively use cap‐independent translation for synthesis of viral proteins.