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Chapter 28 : Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses, and Retrotransposons

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Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses, and Retrotransposons, Page 1 of 2

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Abstract:

Retrotransposons are widespread transposable elements that are closely related to retroviruses. As for all retroids, the replication cycle of retroviruses, retrotransposons, and pararetroviruses includes a reverse transcription step. Reverse transcription of the retroviral genome takes place in the cytoplasm of the infected cell. In retroviruses and retrotransposons, the viral enzymes, including reverse transcriptase (RT), are synthesized as Gag-Pol precursors, while the pol gene of cauliflower mosaic virus (CaMV; the caulimovirus prototype) is expressed separately from the gag gene. It is not only the modified nucleotides of tRNAs, but also those present in the genomic RNA itself might affect the replication of retroviruses and retrotransposons. The identification of such modifications and their possible roles are described in this chapter. Modified nucleotides might be critical for a number of steps in the replication life cycle of retroviruses, plant pararetroviruses, and retrotransposons. The importance of modified nucleotides of the primer tRNA for encapsidation and reverse transcription is well established. It is important to realize that no general conclusion that would be valid for all retroviruses, plant pararetroviruses, and retrotransposons can be drawn regarding the importance of modified nucleotides. Human retroviruses cause several fatal diseases, including AIDS (HIV-1 and HIV-2), leukemia (HTLV-I and HTLV-II), and possibly multiple sclerosis. Obviously, defining the exact roles of modified nucleotides in the replication life cycles of plant pararetroviruses, retrotransposons, and especially retroviruses deserves more attention.

Citation: Marquet R. 1998. Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses, and Retrotransposons, p 517-533. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch28

Key Concept Ranking

DNA Synthesis
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Long Terminal Repeat Retrotransposons
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Equine infectious anemia virus
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Mouse mammary tumor virus
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Equine infectious anemia virus
0.51417875
Mouse mammary tumor virus
0.51417875
Equine infectious anemia virus
0.51417875
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Figures

Image of Figure 1
Figure 1

The retroviral replication life cycle. Reverse transcription, integration, and maturation require viral enzymes encoded by the gene. The steps that are affected by modified nucleotides are indicated by asterisks.

Citation: Marquet R. 1998. Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses, and Retrotransposons, p 517-533. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch28
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Image of Figure 2
Figure 2

Secondary structure of some of the tRNAs used as primers by retroviruses, retrotransposons, and pararetroviruses. The nucleotides that have been proposed to interact with the genomic RNA of retroids (see text) are indicated in white on a black background. In tRNA, *U is an unidentified modified U; in tRNA , A stands for --ribosyl-(1′′-2′)-adenosine-5′′ phosphate. The differences between the two tRNA isoacceptors that are used as primers by murine leukemia virus are indicated.

Citation: Marquet R. 1998. Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses, and Retrotransposons, p 517-533. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch28
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Image of Figure 3
Figure 3

Schematic representation of the process of reverse transcription. RNA and DNA are represented by thin and thick lines, respectively. The DNA region that is being synthesized during each step is shown in black. Capital and lowercase letters are used to indicate regions in the RNA (PBS, U5, ...) and in the DNA [u3(–), u3(+), . . .], respectively. The — and + refer to the minus and plus DNA strands, respectively. U3 and U5 are unique sequences present at the 3′ or 5′ end of the genomic RNA, respectively, while R is a repeated sequence present at both ends of the genomic RNA. PPT is the polypurine tract. In step I, reverse transcription is initiated from the 3′ hydroxyl end of the primer tRNA annealed to the PBS, and proceeds until RT reaches the 5′ end of the template. The corresponding cDNA is named minus-strand strong-stop DNA. After degradation of the 5′ end of the template by RNase H and the first-strand transfer, synthesis of the minus strand resumes (step II). The plus-strand synthesis is initiated from the PPTs that are generated by RNA regions resistant to the RNase H degradation (step III). Depending on the retrovirus, one or two PPTs may be used as primers. When the polymerizing plus-strand DNA chain reaches the end of the minus-strand DNA template, RT copies the primer tRNA until it is stopped by a modified nucleoside. After the second-strand transfer, which leads to a circular intermediate, DNA synthesis resumes on both strands (step IV). The nicks and overhangs are repaired by the host enzymes to yield regular double-stranded DNA (step V).

Citation: Marquet R. 1998. Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses, and Retrotransposons, p 517-533. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch28
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Image of Figure 4
Figure 4

Secondary structure model of the viral RNA/tRNA (template/primer) complex. The sequences of the viral RNA and tRNA are indicated by upper- and lowercase letters, respectively. The modified nucleotides of tRNA are highlighted and the PBS of the viral RNA is boxed. Adapted from .

Citation: Marquet R. 1998. Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses, and Retrotransposons, p 517-533. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch28
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Image of Figure 5
Figure 5

Ribosomal frameshifting. The −1 (A) and +1 (B) frameshiftings are illustrated with HIV-1 and Tyl, respectively. The A and P ribosomal sites are schematically represented.

Citation: Marquet R. 1998. Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses, and Retrotransposons, p 517-533. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch28
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Tables

Generic image for table
Table 1

−1 frameshift signals in retroviruses

Citation: Marquet R. 1998. Importance of Modified Nucleotides in Replication of Retroviruses, Plant Pararetroviruses, and Retrotransposons, p 517-533. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch28

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