Mutations conferring streptolydigin resistance onto Escherichia coli RNA polymerase have been found exclusively in the subunit (Heisler, L. M., Suzuki, H., Landick, R., and Gross, C. A.(1993) J. Biol. Chem. 268, 25369-25375). We report here the isolation of a streptolydigin-resistant mutation in the E. coli rpoC gene, encoding the ` subunit. The mutation is the Phe Ser substitution, which occurred in an evolutionarily conserved segment of the ` subunit. The homologous segment in the eukaryotic RNA polymerase II largest subunit harbors mutations conferring -amanitin resistance. Both streptolydigin and -amanitin are inhibitors of transcription elongation. Thus, the two antibiotics may inhibit transcription in their respective systems by a similar mechanism, despite their very different chemical nature.

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