Tn10 protects itself at two levels from fortuitous activation by external promoters.

Tn10 rarely transposes, primarily because its IS10-encoded transposase protein is synthesized infrequently. Since the 5' end of the transposase gene is immediately adjacent to flanking host sequences, insertion of Tn10 into an actively transcribed operon could conceivably result in dramatically increased transposition. We show here that Tn10 is protected from such fortuitous activation; high levels of transcription from an upstream promoter actually decrease its rate of transposition. Protection operates at two levels. First, externally-initiated transcripts yield only a small amount of additional transposase protein, primarily because of inhibition at a posttranscriptional level. We suggest that the transposase gene start codon is sequestered in an mRNA secondary structure not present in transcripts initiated at the normal promoter. Second, transcription per se across an IS10 terminus inhibits its activity, thus negating any small transposase increase. These observations provide additional evidence that Tn10 has evolved specific mechanisms for keeping its transposition activity low.