Interferon‐Mediated Inhibition of Cell‐Free‐Protein Synthesis in Response to Double‐Stranded RNA

The inhibition by double‐stranded RNA (dsRNA) of the translation of encephalomyocarditis virion RNA (EMC RNA) in extracts from interferon‐treated mouse L‐cells has been investigated. In particular, we have found that the addition of small amounts of dialysed cell sap from interferon‐treated cells to cell‐free systems from control cells renders them more sensitive to inhibition by dsRNA. This has provided an assay for the component(s) involved in the inhibition. The translation of both viral and non‐viral messenger RNAs is inhibited by dsRNA in the presence of interferon cell sap. The concentration of dsRNA required for inhibition, however, varies with the salt concentration used. The lower sensitivity of the control cell‐free system to dsRNA does not reflect a higher level of dsRNA‐specific nuclease, nor is the inhibition by interferon cell sap and dsRNA reversed by the addition of tRNA. There is an enhanced breakdown of the EMC RNA message in the inhibited systems. It is not yet clear, however, whether this reflects the activity of a dsRNA‐activated single‐strand‐RNA‐specific nuclease, or merely the degradation of unused message in the dsRNAinhibited system. Interestingly, the abnormal distribution of polypeptide products synthesised in response to EMC RNA in systems inhibited by interferon cell sap and dsRNA is apparently identical to that obtained on translation of this RNA in cell‐free systems from interferon‐treated, vacciniavirus‐infected L‐cells.