Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic release factor 1 to modulate suppression of translational termination.

Abstract

The pol (for polymerase) gene of the murine leukemia viruses (MuLVs) is expressed in the form of a large Gag-Pol precursor protein by the suppression of translational termination, or enhanced readthrough, of a UAG stop codon at the end of gag. A search for cellular proteins that interact with the reverse transcriptase of Moloney MuLV resulted in the identification of eRF1, the eukaryotic translation release factor 1. The proteins bound strongly in vitro, and the overexpression of eRF1 resulted in the RT-dependent incorporation of the protein into assembling virion particles. The overexpression of RT in trans enhanced the translational readthrough of a reporter construct containing the Gag-Pol boundary region. Noninteracting mutants of RT failed to synthesize adequate levels of Gag-Pol and could not replicate. These results suggest that RT enhances suppression of termination and that the interaction of RT with eRF1 is required for an appropriate level of translational readthrough.