Release of Interferon-Induced Translation Inhibition by tRNA in Cell-Free Extracts from Mouse Erythroleukemia Cells

Preincubated cell-free lysates from interferon-treated Friend-virus-transformed mouse proerythro-blasts have been used to study the mechanism of the antiviral effect of mouse interferon. Similar to preincubated cell-free protein-synthesizing systems derived from other interferon-treated murine cells, translation of globin and encephalomyocarditis virus (EMC) RNA is inhibited. In a fractionated cell-free system run-off ribosomes prepared from interferon-treated and control proerythroblasts were of the same activity. Addition of tRNA from eukaryotic cells to the reaction mixture could restore the translation capacity for EMC and globin RNA. Various purified tRNA species were tested for their capacity to restore the translation activity: tRNALys2 from rabbit liver but not the isoaccepting tRNALys3 showed activity to release the inhibition. The efficiency to restore the translation activity was, however, less than with total tRNA from rabbit liver, indicating that other tRNA species are also able to restore the translation activity in extracts from interferon-treated mouse proerythroblasts. tRNAVal1 and partially purified tRNASer and tRNALeu species from rabbit liver had no restoring activity. tRNA modified by periodate treatment could also restore translation activity, although with reduced efficiency. The translation inhibition and release by tRNA in preincubated extracts from interferon-treated mouse proerythroblasts and uninfected L-cells seems to be caused basically by the same molecular mechanism. This phenomenon, however, clearly contrasts with the inhibition of translation of exogenous mRNA observed with extracts from interferon-treated and vaccinia-infected L-cells. The translation inhibition in extracts from interferon-treated and vaccinia-infected cells cannot be reversed by tRNA and an alternative molecular mechanism must therefore be considered.