Structural Biochemistry/Ribosome Mediated Translation Initiation for Vesicular Stomatitus Virus
Negative sense viral mRNAs are translated while host mRNA are inhibited. However, unlike internal ribosome entry sites that bypass the cap dependent system, negative sense viral mRNAs are 5’ capped, polyadenylated, and structurally identical to the host mRNA. How does the host distinguish between cellular RNA and viral RNA?
Vesicular stomatitis virus (VSV) is a negative strand virus that inhibits host protein synthesis by hypophosphorylation of the eIF4E-binding protein 1 causing sequestration of eIF4E and inhibiting 5’ cap dependent translation. It also diminishes the ribosomal pool by blocking export of pre-ribosomal RNA from the nucleus and inhibiting transcription of rRNA. It is still efficiently translated after these alterations in cellular machinery.
Through fluorescence microscopy of siRNA targeted screens for ribosomal proteins, it was found the rpL40 was responsible for viral translation. To determine the mechanism of translation control by rpL40, the formation of ribosomes on VSV mRNA was compared to a standard mRNA. It was found that the viral mRNA when depleted of rpL40 had no mRNA bound to 60S ribosomes indicating that rpL40 is a constituent of the large ribosome. The use of this mechanism is dependent on a cis-acting RNA element and reveals that the ribosome can act as a regulator of translation aside from its catalytic role.
- Si-Ying Lee, Amy and Burdeinick-Kerr, Rebeca, and Whelan, Sean P.J. PNAS. A Ribosome-Specialized Translation Initiation Pathway is Required for Cap-dependent Translation of Vesicular Stomatitis Virus mRNAs. October 2012.