A tentative initiation inhibitor of chromosomal heterogeneous RNA synthesis

The nucleoside analogue 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole inhibits labelling of chromosomal, high molecular weight RNA in the salivary gland cells of Chironomus tentans but does not interfere with the synthesis of ribosomal RNA and chromosomal low molecular weight RNA. When DRB2 was added after an initial labelling period (pulse-chase experiment) the radioactivity diminished preferentially in the lower molecular weight region of the HnRNA spectrum. After short chase periods the activity decreased moderately, or even increased, in the higher molecular weight region of the spectrum (75–100 S). After prolonged chases there was an overall and similar reduction in the activity in the whole HnRNA distribution. If the glands were preincubated in DRB for a short period before exposure to radioactive precursors, the label was again diminished more in HnRNA of low molecular weight than in that of higher molecular weight. When α-amanitin or actinomycin D, both known to be inhibitors of RNA chain elongation, replaced DRB in pulse-chase experiments, labelling of HnRNA was depressed in all size classes to the same extent. The accumulated data suggest that DRB acts, in explanted salivary gland cells, at the polymerase level by interfering with the initiation of chromosomal HnRNA synthesis.