Peer-Reviewed Journal Details
Mandatory Fields
Ren, Q,Wang, QS,Firth, AE,Chan, MMY,Gouw, JW,Guarna, MM,Foster, LJ,Atkins, JF,Jan, E
2012
January
Proceedings of The National Academy of Sciences of The United States of America
Alternative reading frame selection mediated by a tRNA-like domain of an internal ribosome entry site
Validated
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Optional Fields
frameshifting Israeli acute paralysis virus protein synthesis pseudoknot genetic recoding CRICKET PARALYSIS VIRUS STALI-INTESTINE-VIRUS TRANSLATION INITIATION FUNCTIONAL-ANALYSIS PROTEIN-SYNTHESIS CAPSID PROTEIN COMPLEX EIF4F VIRAL IRES DICISTROVIRUSES ELONGATION
109
630
639
The dicistrovirus intergenic region internal ribosome entry site (IRES) utilizes a unique mechanism, involving P-site tRNA mimicry, to directly assemble 80S ribosomes and initiate translation at a specific non-AUG codon in the ribosomal A site. A subgroup of dicistrovirus genomes contains an additional stem-loop 5'-adjacent to the IRES and a short open reading frame (ORFx) that overlaps the viral structural polyprotein ORF (ORF2) in the +1 reading frame. Using mass spectrometry and extensive mutagenesis, we show that, besides directing ORF2 translation, the Israeli acute paralysis dicistrovirus IRES also directs ORFx translation. The latter is mediated by a U: G base pair adjacent to the P-site tRNA-mimicking domain. An ORFx peptide was detected in virus-infected honey bees by multiple reaction monitoring mass spectrometry. Finally, the 5' stem-loop increases IRES activity and may couple translation of the two major ORFs of the virus. This study reveals a novel viral strategy in which a tRNA-like IRES directs precise, initiator Met-tRNA-independent translation of two overlapping ORFs.
DOI 10.1073/pnas.1111303109
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