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TRNA-mRNA mimicry drives translation initiation from a viral IRES.

ABSTRACT: Internal ribosome entry site (IRES) RNAs initiate protein synthesis in eukaryotic cells by a noncanonical cap-independent mechanism. IRESes are critical for many pathogenic viruses, but efforts to understand their function are complicated by the diversity of IRES sequences as well as by limited high-resolution structural information. The intergenic region (IGR) IRESes of the Dicistroviridae viruses are powerful model systems to begin to understand IRES function. Here we present the crystal structure of a Dicistroviridae IGR IRES domain that interacts with the ribosome's decoding groove. We find that this RNA domain precisely mimics the transfer RNA anticodon-messenger RNA codon interaction, and its modeled orientation on the ribosome helps explain translocation without peptide bond formation. When combined with a previous structure, this work completes the first high-resolution description of an IRES RNA and provides insight into how RNAs can manipulate complex biological machines.

SUBMITTER: Costantino DA

PROVIDER: S-EPMC2748805 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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tRNA-mRNA mimicry drives translation initiation from a viral IRES.

Costantino David A DA Pfingsten Jennifer S JS Rambo Robert P RP Kieft Jeffrey S JS

Nature structural & molecular biology 20071223 1

Internal ribosome entry site (IRES) RNAs initiate protein synthesis in eukaryotic cells by a noncanonical cap-independent mechanism. IRESes are critical for many pathogenic viruses, but efforts to understand their function are complicated by the diversity of IRES sequences as well as by limited high-resolution structural information. The intergenic region (IGR) IRESes of the Dicistroviridae viruses are powerful model systems to begin to understand IRES function. Here we present the crystal struc ...[more]

PMID: 18157151

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