Unrelated leader sequences can efficiently promote human tRNA gene transcription.

The 5'-leader sequence of a human tRNA gene encoding the major tRNA(IACVa 1) species was replaced by several unrelated sequences of human and bacterial origin. Transcription in a HeLa cell extract revealed an extragenic control region (ECR) between positions -51 and -16. Competition assays demonstrate that the wild-type ECR acts as a positive modulator of transcription factor binding. The amount of active transcription complex formed is shown to be dependent on the ECR, whereas the stability of transcription complexes formed under the control of wild-type and mutant ECRs seems not to be affected. One bacterial DNA provided transcription controlling properties indistinguishable from those of the natural human leader sequence. The poor homology between these two sequences indicates that ECRs of human tRNA genes do not consist of highly conserved boxes like intragenic control regions, but of fairly individual DNA elements.