Certain viruses are considered mobile genetic elements because they use transposition mechanisms to integrate their genomes into that of their host cell. However, unlike transposons, these viruses encode proteins that package their genetic information into virus particles that can infect other cells. Many of the viruses that insert themselves into a host chromosome do so by employing one of the first two mechanisms listed in Table 5–4; namely, by behaving like DNA-only transposons or like retroviral-like retrotransposons. Indeed, much of our knowledge of these mechanisms has come from studies of particular viruses that employ them.
Transposition has a key role in the life cycle of many viruses. Most notable are the retroviruses, which include the human AIDS virus, HIV. Outside the cell, a retrovirus exists as a single-strand RNA genome packed into a protein shell or capsid along with a virus-encoded reverse transcriptase enzyme. During the infection process, the viral RNA enters a cell and is converted to a double-strand DNA molecule by the action of this crucial enzyme, which is able to polymerize DNA on either an RNA or a DNA template (Figure 5–62). The term retrovirus refers to the virus’s ability to reverse the usual flow of genetic information, which normally is from DNA to RNA (see Figure 1–4).
Once the reverse transcriptase has produced a double-strand DNA molecule, specific sequences near its two ends are recognized by a virus-encoded
Figure 5–62 The life cycle of a retrovirus. The retrovirus genome consists of an RNA molecule (blue) that is typically between 7000 and 12,000 nucleotides in length. It is packaged inside a protein capsid, which is surrounded by a lipid-based envelope that contains virus-encoded envelope proteins (green). Inside an infected cell, the enzyme reverse transcriptase (red circle) first makes a DNA copy of the viral RNA molecule and then a second DNA strand, generating a double-strand DNA copy of the RNA genome. The integration of this DNA double helix into the host chromosome is then catalyzed by a virus-encoded integrase enzyme. This integration is required for the synthesis of new viral RNA molecules by the host-cell RNA polymerase, the enzyme that transcribes DNA into RNA (discussed in Chapter 6).
transposase called integrase. Integrase then inserts the viral DNA into the chromosome by a mechanism similar to that used by the cut-and-paste DNA-only transposons (see Figure 5–61).
Retroviral-like Retrotransposons Resemble Retroviruses, but Lack a Protein Coat
A large family of transposons called retroviral-like retrotransposons (see Table 5–4) move themselves in and out of chromosomes by a mechanism that is similar to that used by retroviruses. These elements are present in organisms as diverse as yeasts, flies, and mammals; unlike viruses, they have no intrinsic ability to leave their resident cell but are passed along to all descendants of that cell through the normal processes of DNA replication and cell division. The first step in their transposition is the transcription of the entire transposon, producing an RNA copy of the element that is typically several thousand nucleotides long. This transcript, which is translated as a messenger RNA by the host cell, encodes a reverse transcriptase enzyme. This enzyme makes a double-strand DNA copy of the RNA molecule via an RNA–DNA hybrid intermediate, precisely mirroring the early stages of infection by a retrovirus (see Figure 5–62). Like a retrovirus, the linear, double-strand DNA molecule then integrates into a site on the chromosome using an integrase enzyme that is also encoded by the element. The structure and mechanisms of these integrases closely resemble those of the transposases of DNA-only transposons.
A Large Fraction of the Human Genome Is Composed of Nonretroviral Retrotransposons