Retrovirus transposition

Some well-characterized eukaryotic DNA transposons from sources as diverse as yeast and fruit flies have a structure very similar to that of retroviruses these are sometimes called retrotransposons (Fig. 26-33). Retro-transposons encode an enzyme homologous to the retroviral reverse transcriptase, and their coding regions are flanked by LTR sequences. They transpose from one position to another in the cellular genome by means of an RNA intermediate, using reverse transcriptase to make a DNA copy of the RNA, followed by integration of the DNA at a new site. Most transposons in eukaryotes use this mechanism for transposition, distinguishing them from bacterial transposons, which move as DNA directly from one chromosomal location to another (see Fig. 25-43). 

Many eukaryotic transposons are related to retroviruses, and their mechanism of transposition includes an RNA intermediate. 

Transposition of DNA, which is discussed in Chapter 27, Section D,4, may seem to be a rare and relatively unimportant event in our body cells. However, transposon DNA accounts for 35% or more of the human genome740 and apparently plays a major role in evolution. Like other transposons, the DNA sequences known as retrotransposons also move about within DNA. However, they use an indirect mechanism that involves synthesis of mRNA and reverse transcription.740 741 The reverse transcribed complementary DNA may be inserted back into the genome at new locations. The necessary chemical reactions parallel those involved in the replication of retroviruses (Fig. 28-23, 28-24). Retrotransposens, truncated retrotransposons, and related sequences constitute as much as 16% of the human genome.741... 

Retroviruses Are RNA Viruses That Replicate through a DNA Intermediate Hepatitis B Virus Is a DNA Virus That Replicates through an RNA Intermediate Some Transposable Genetic Elements Encode a Reverse Transcriptase That Is Crucial to the Transposition Process... 

All of the mammalian transposable elements that have been characterized to date seem to be the result of transpositions that proceeded through an RNA intermediate. This process is known as retrotransposition or retroposition. Three classes of these retrotransposable elements are known in mammals (1) SINEs, or short interspersed repeated sequences such as the human Alu family and rodent Bl (2) LINEs, or long interspersed repeated sequences such as LI in a variety of mammalian species and (3) retrovirus-like elements, such as THE 1 in humans and mys and IAP in rodents. Retrovirus-like elements have long terminal repeats (LTRs) that often surround two open reading frames (ORFs) like those of retroviruses, but they lack the ability to leave one cell and enter another. LINEs also have two ORFs, but have no LTRs. SINEs have no LTRs and no ORFs. Transposition of all of these elements must involve reverse transcription of the RNA intermediate in some cases the required reverse transcriptase is apparently encoded by the element itself. 

Many retrotransposons encode proteins that are homologous with the gag and pol genes of retroviruses.23 Because the function of the reverse transcriptase enzyme may be necessary for the transposition of these elements, it is important to search for sequence similarities in the repetitive elements that are newly isolated. 

Many DDE transposases carry a DNA sequence-specific binding domain in their N-terminal regions and at least one domain involved in multimerization. Generally, the catalytic domain is located in the C-terminal part of the protein. The DDE domain is by far the most studied and best understood catalytic motif involved in transposition. It is found in many different types of transposon from retroviruses to Tc-Mariner, bacterial ISs, and transposons (4). 

Cellular oncogenes (VI) can be activated by amplification, by single point mutations, or by transposition. Slowly transforming retroviruses do not contain viral oncogenes but stimulate expression of cellular oncogenes by insertional mutagenicity. Radiation and chemical carcinogens also activate cellular onco-... 

As noted above, LTR retrotransposons encode reverse transcriptase and Integrase. By analogy with retroviruses, these mobile elements are thought to move by a copy-and-paste mechanism whereby reverse transcriptase converts an RNA copy of a donor-site element into DNA, which Is Inserted Into a target site by integrase. The experiments depicted in Figure 10-14 provided strong evidence for the role of an RNA intermediate in transposition of Ty elements. 

Transposable elements have been demonstrated in many eukaryotes, including maize. Drosophila, yeast, and bacteria. Gene transposition in eukaryotic systems presents some strong similarities to and some distinct differences from transposition in bacteria. The first major distinction is that integration and excision are distinct processes in eukaryotes. Thus, the transposable element can be isolated in free form, often as a double-strand circular DNA. Second, replication of that DNA often involves the synthesis of an RNA intermediate. Both of these properties are seen in the retroviruses of vertebrates, perhaps the most widely studied class of eukaryotic transposable elements. 

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