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Mechanisms of Translation Regulation

Understanding Viral Gene Expression

Understanding viral gene expression

Viral mRNA can efficiently hijack host ribosomes during infection for translation of proteins necessary for virus propagation. Initiation of translation is a key step, during which the coding region of mRNA, open reading frame, gets properly positioned on the ribosome. Cryo-EM (electron cryo-microscopy) structures of the ribosome-bound Taura syndrome virus (TSV) messenger RNA (red) reveal a structural mechanism of initiation on viral mRNAsDicistroviridae intergenic sequences, known as the internal ribosome entry sites (IRES), initiate translation by binding their tRNA-mRNA–like element - pseudoknot I (PKI) - in the aminoacyl-tRNA site (A site) of the ribosome, as described in Koh et al. "Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA-like structural element in the ribosomal decoding center" (Proc Natl Acad Sci U S A. 2014). 
Following the initial binding (INIT), the viral IRES mRNA is translocated by elongation factor eEF2 from the A to P site - to allow binding of the first tRNA and translation initiation. Cryo-EM allowed us capturing an ensemble of intermediate structures at 3.5- to 4.2-A resolution (structures I through V). They describe a nearly complete trajectory of TSV IRES translocation, bringing several new insights into ribosomal dynamics and the role of translocase eEF2 (Abeyrathne et al. "Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome". eLife. 2016). 
Click on the image above to see a more detailed view of TSV IRES translocation by eEF2.