Regulation of the Primary Expression of the Early Adenovirus Transcription Units

Abstract

The time course of appearance of transcriptional activity from 5 early adenovirus type 2 transcription units was determined. RNA complementary to region 1A (1-4.4 map units), the 1st region to be transcribed, was detectable at 45 min after infection [of human cervical carcinoma HeLa cells]; a maximal rate of RNA synthesis was reached 3 h after infection and was maintained thereafter for at least 6 h. RNA from region 2 (75-56 map units), which encodes the mRNA for the 72,000-dalton DNA-binding protein, was the last to be synthesized; transcription commenced at about 2 h postinfection, reached a maximum at 7 h and then declined. Transcription of regions 3 (76-86 map units) and 4 (99-91 map units) reached a maximal value at 3 h postinfection. Rates of RNA synthesis from these regions declined over the next 6 h. The decline of transcription from regions 2 and 4 appeared to be a specific repression of these transcription units. The repression did not occur in absence of protein synthesis, suggesting that a viral protein might be involved. Transcription of all early regions was initiated and continued for at least 2-3 h in cells treated with cycloheximide or emetine before and during infection, suggesting that at least initiation of RNA synthesis from the 5 early adenovirus type 2 transcription units does not depend on formation of a viral protein. mRNA was formed in the absence of protein synthesis that hybridized to DNA fragments representing each of the 5 early transcription units. Increase in mRNA accumulation in the presence of cycloheximide (or emetine) does not appear to be due to increased RNA synthesis; either increased mRNA stability or increased efficiency of nuclear RNA processing must occur.