Background: The ubiquitous multimeric RNA polymerases contain two large, conserved subunits, of which the  subunit has been implicated in all three stages of transcription. We have previously described a genetic system involving random, PCR-mediated mutagenesis of the region of rpoB encoding the C-terminal 116 amino acids of the  subunit of Escherichia coli RNA polymerase and the characterization of dominant-negative mutations. This study identified the invariant motif GEME (residues 1271→1274; Cromie et al. 1999). Starting with three of these GEME-motif lethal mutations (G1271E, G1271V, M1273V), we have selected for intragenic suppressors, located within the same 3 0 -region, that prevent expression of the trans-dominant phenotype.