Streptolydigin-resistant mutants in an evolutionarily conserved region of the β′ subunit of Escherichia coli RNA polymerase

Mutations conferring streptolydigin resistance onto Escherichia coli RNA polymerase have been found exclusively in the β 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 β′ subunit. The mutation is the Phe⁷⁹³ → Ser substitution, which occurred in an evolutionarily conserved segment of the β′ subunit. The homologous segment in the eukaryotic RNA polymerase II largest subunit harbors mutations conferring α-amanitin resistance. Both streptolydigin and α-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.