Adenovirus Major Late

Watt, F. and Molloy, P.L. (1988) Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes and Development, 2, 1136-1143. 

Sawadogo, M. Roeder, R.G. (1985). Interaction of a gene-specific transcription factor with the adenovirus major late promoter upstream of the TATA box region. Cell 43, 165-75. 

Figure 30.7 shows the transcription pattern of early and late adenoviral transcription units which are transcribed from both strands. Adenoviral mRNAs are processed by the cellular machinery and contain 50 methyl guanosine caps and poly(A) tails. The adenovirus major late promoter is responsible for directing the transcription of a single precursor transcript, which gives rise to different mRNA classes that terminate at one of five polyadenylation signals. These mRNAs are then differentially spliced to remove internal portions of the coding sequence. 

The ability of the histone-like TAFs to form an octamer-like structure raises the possibility that the TAF octamer may wrap promoter DNA in a manner similar to the nucleosome (Hoffmann et al., 1997 Oelgeschlager et al., 1996). This hypothesis is supported by the resemblance of DNase I footprinting patterns of TFIID on the Adenovirus Major Late (AdML) promoter to those of nucleosomal DNA. However, the arginine side chains in histones that form primary contacts with DNA are not conserved in TAFs (Luger et al., 1997). Therefore, the histone fold domain interaction may be used only for the formation of a compact structure and is not necessarily involved in DNA wrapping. 

In four cases, immediate upstream sequences do have effects on the efficiency of transcription in vitro. Sequential upstream deletions of the adenovirus major late promoter indicated that sequences between -97 and -62 exerted a threefold effect on the efficiency of transcription in vitro (Hen et al., 1982). A similar analysis of the adenovirus EIII control region indicated that sequences upstream of... 

Phil Sharp and Leonard Guarente showed that at least four transcription factors are required in addition to polymerase II for initiation from the major late promoter of adenovirus. In vitro studies indicate that these factors assemble in an orderly fashion (see fig. 28.12b). First the TFIID complex binds to the TATA box. Sequential binding of TFIIA, TFIIB, RNA polymerase II, and TFIIE follow. It is believed that this multifactor complex functions for a large number of eukaryotic promoters that contain TATA boxes. 

Synthesis and processing of adenovirus transcripts. The adenovirus genome contains six promoters which give rise to multiple transcripts. The major late promoter is especially active and generates several classes of transcripts which terminate at any one of five polyadenylation signals. Through an elaborate alternative splicing pathway, each class of major late transcript is processed to include the same aminoterminal protein sequences linked to various carboxy terminal residues. 

Figure 10.1-4. The adenovirus genome. The early (E1-E4) and late (L1-L5) transcription units are identified by the arrows. The inverted terminal repeats (ITRs), packaging sequence ( /), and major late promoter (MLP) are also shown. (Adapted from Ref. 26.)...

Dahmus, M. E., and Kedinger, C., 1983, Transcription of adenovirus-2 major late promoter inhibited by monoclonal antibody directed against RNA polymerase IIo and IIa, J. Biol. Chem. 258 2303-2307. 

Fraser, N. W., Nevins, J. R., Ziff, E., and Darnell, J. E., 919a. The major late adenovirus type-2 transcription unit Termination is downstream from the last poly(A) site, J. Mol. Biol. 129 643-656. 

Hu, S.-L., and Manley, J. L., 1981, DNA sequence required for initiation of transcription in vitro from the major late promoter of adenovirus 2, Proc. Natl. Acad. Sci. USA 78 820-824. 

Akusjarvi, G., and Persson, H., 1981, Controls of RNA splicing and termination in the major late adenovirus transcription unit. Nature London) 292 420. 

Miller, J. S., Ricciardi, R. P., Roberts, B. E., Paterson, B. M., and Mathews, M. B., 1980, Arrangement of messenger RNAs and protein coding sequences in the major late transcription unit of adenovirus, J. Mol. Biol. 142 455. 

Shaw, A. R., and Ziff, E., 1980, Transcripts from the adenovirus 2 major late promoter yield a single early family of V coterminal mRNAs and five late families. Cell 22 905. 

Ziff, E., and Evans, R., 1978, Coincidence of the promoter and capped 5 terminus of RNA from the adenovirus 2 major late transcription unit. Cell 15 1463. 

Adenovirus has a single promoter for all RNA made late in the cycle of infection. The primary transcripts terminate at five major polyadenylation sites. Each termination site influences the splicing pattern by allowing particular in-trons or intron termini to be present or not. The five sets are not used with equal frequency, with the result that most mRNAs encoding various genes are not the same. This is the primary mechanism for determining the relative amounts of the different structural proteins synthesized late in the adenovirus life cycle. 

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