Telomerase reverse transcriptase transcripts

Kyo S, Takakura M, Taira T, Kanaya T, Itoh H, et al. 2000. Spl cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res. 28 669-77... 

Reverse transcription (which occurs in both prokaryotes and eukaryotes) is the synthesis of DNA from an RNA template. A class of RNA viruses, called retroviruses, are characterized by the presence of an RNA-dependent DNA polymerase (reverse transcriptase). The vims that causes AIDS, Human Immunodeficiency Virus (HIV), is a retro-vims. Because nuclear cell division doesn t use reverse transcriptase, the most effective anti-HIV drugs target reverse transcriptase, either its synthesis or its activity. Telomerase, discussed in the previous section, is a specialized reverse transcriptase enzyme. See Figure 12-5. 

The process of transcription can also occur in reverse, from RNA to DNA, when the sequence coded in RNA is transcribed into antisense DNA by reverse transcriptase enzymes first discovered by Temin and Mizutani [18] and Baltimore [19]. Further integrase enzymes insert the DNA sequence into the native DNA. This is the mechanism by which viruses infect their host organisms and can be stopped by antiviral drugs, such as azidothymine (AZT) that inhibits F1IV reverse transcriptase. Other processes such as the extension of telomeres at the ends of chromosomes by telomerase, to control programmed cell death, use the same mechanism. 

Some cells that lack telomerase activity, on the other hand, still have a high level of hTERT transcription. In these cases, regulation at the level of alternative splicing leads to skipping of exons that encode reverse transcriptase function, so any translation product would not give an active enzyme [47]. 

Cytotoxicity occurs as a result of the molecular interactions of an alkaloid with one or several important targets present in a cell (Figures 1 and 2). The main targets include DNA, RNA, and the associated enzymes and processes (i.e., replication, repair, transcription, DNA polymerase, RNA polymerase, reverse transcriptase, repair enzymes, topoisomerase, telomerase), protein biosynthesis, protein conformation, biomembranes, and membrane proteins (for reviews, see (10,11,16)). 

Intercalating compounds also directly inhibit DNA replication and transcription. RNA is basically single stranded, but most RNA molecules have double-stranded stem structures because of complementary base pairing. These double-stranded regions can also be intercalated. Therefore, many intercalating SM are also inhibitors of DNA and RNA polymerases, of reverse transcriptase, and even of DNA topoisomerases and possibly telomerase. 

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