Transcription of the 5′-Terminal Cap Nucleotide by RNA-Dependent DNA Polymerase: Possible Involvement in Retroviral Reverse Transcription

Volloch, Vladimir; Schweitzer, Bruce; Rits, Sophia

doi:10.1089/dna.1995.14.991

Cited by 19 publications

(18 citation statements)

References 15 publications

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“…Retroviral RT has previously been reported to reverse-transcribe the cap (Hirzmann et al 1993;Volloch et al 1995). We also present evidence for reverse transcription of a cap in L1-mediated retrotransposition, of processed pseudogenes from the HERV-W family of human endogenous retroviruses (Costas 2002;Pavlicek et al 2002a).…”

Section: Genome Research 2257supporting

confidence: 67%

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The human L1 promoter: Variable transcription initiation sites and a major impact of upstream flanking sequence on promoter activity

Lavie

Maldener²,

Brouha³

et al. 2004

Genome Res.

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Human L1 elements are non-LTR retrotransposons that comprise ∼17% of the human genome. Their 5Ј-untranslated region (5Ј-UTR) serves as a promoter for L1 transcription. Now we find that transcription initiation sites are not restricted to nucleotide +1 but vary considerably in both downstream and upstream directions. Transcription initiating upstream explains additional nucleotides often seen between the 5Ј-target site duplication and the L1 start site. A higher frequency of G nucleotides observed upstream from the L1 can be explained by reverse transcription of the L1 RNA 5Ј-CAP, which is further supported by extra Gs seen for full-length HERV-W pseudogenes. We assayed 5Ј-UTR promoter activities for several full-length human L1 elements, and found that upstream flanking cellular sequences strongly influence the L1 5Ј-UTR promoter. These sequences either repress or enhance the L1 promoter activity. Therefore, the evolutionary success of a human L1 in producing progeny depends not only on the L1 itself, but also on its genomic integration site. The promoter mechanism of L1 is reminiscent of initiator (Inr) elements that are TATA-less promoters expressing several cellular genes. We suggest that the L1 5Ј-UTR is able to form an Inr element that reaches into upstream flanking sequence.

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Section: Genome Research 2257supporting

confidence: 67%

“…Basically, the cap is a modified GTP. It is known that retroviral reverse transcriptases can reverse-transcribe the cap structure (Hirzmann et al 1993;Volloch et al 1995). As L1 RNA is most likely transcribed by RNA Polymerase II , a cap structure is very likely added to the L1 RNA 5Ј-end.…”

Section: Variable Transcriptional Start Sites In Human L1 Elementsmentioning

confidence: 99%

The human L1 promoter: Variable transcription initiation sites and a major impact of upstream flanking sequence on promoter activity

Lavie

Maldener²,

Brouha³

et al. 2004

Genome Res.

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show abstract

“…Finally, it has recently been suggested that the 5Ј cap structure of mRNA may have contributed to the proliferation of retrotransposons in eukaryotes (36). Various RTs have been shown to copy the G residue of the 5Ј cap (37,38), which may explain the variable number of G residues found at the 5Ј junction of some elements (36). Our data suggest that these 5Ј caps would also not inhibit end-to-end jumps.…”

Section: Discussionmentioning

confidence: 62%

End-to-End Template Jumping by the Reverse Transcriptase Encoded by the R2 Retrotransposon

Bibiłło¹,

Eickbush

2004

Journal of Biological Chemistry

104

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The reverse transcriptase encoded by the non-long terminal repeat retrotransposon R2 has been shown to be able to jump from the 5-end of one RNA template (the donor) to the 3-end of a second RNA template (the acceptor) in the absence of preexisting sequence identity between the two templates. These jumps between RNA templates have similarity to the end-to-end template jumps described for the RNA-directed RNA polymerases encoded by certain RNA viruses. Here we describe for the first time the mechanism by which such end-to-end template jumps can occur. Most template jumps by the R2 reverse transcriptase are brought about by the enzyme's ability to add nontemplated (overhanging) nucleotides to the cDNA when it reaches the end of the donor RNA. The enzyme then anneals these overhanging nucleotides to sequences at the 3-end of the acceptor RNA. The annealing is most efficient if it involves the terminal nucleotide(s) of the acceptor RNA but can occur to sites at least 5 nucleotides from the 3-end. These end-to-end jumps are similar to steps proposed to be part of the integration reaction of non-long terminal repeat retrotransposons and can explain chimeric integration products derived from multiple RNA templates.One of the most abundant classes of mobile elements found in eukaryotic genomes is non-LTR 1 retrotransposons. These elements, also referred to as LINE-like elements or retroposons, use a relatively simple mechanism of reverse transcribing RNA templates into DNA for insertion into the genome. In the first step, the target chromosomal DNA is cleaved by an element-encoded endonuclease. The RNA-directed DNA polymerase encoded by the element then uses the free end of the cleaved target DNA as the primer to initiate reverse transcription starting at the 3Ј-end of the element's RNA transcript. This process has been termed target (DNA)-primed reverse transcription (TPRT) (1). Whereas the cleavage that initiates the TPRT reaction could potentially be single-stranded (i.e. a DNA nick) or double-stranded (i.e. a DNA break), in the two systems studied in vitro the cleavage has been shown to be a DNA nick (1, 2). It has been suggested that a short region of the RNA template can anneal to the DNA immediately downstream of the nicked site, thus aiding the initiation of reverse transcription (3). However, such annealing is not required in the most extensively characterized element, the R2 element from Bombyx mori (4 -6).We are conducting a systematic study of the catalytic properties of the reverse transcriptase (RT) encoded by the R2 element (7,8). Perhaps the most dramatic difference between R2 RT and the RT encoded by LTR retrotransposons and retroviruses is the ability of R2 RT to jump from the 5Ј-end of one RNA template to the 3Ј-end of a second RNA template. This continuous polymerization of cDNA on noncontinuous RNA templates differs dramatically from the template switching reaction associated with retroviral cDNA synthesis. Retroviral template switches occur through catalytic removal of the donor RNA from the cDNA s...

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“…Finally, the sequence of the human L1 element provides presumptive evidence for capping. Previous in vitro studies have shown that various RTs can readily copy the G residue comprising the cap, in spite of its unusual 5Ј-5Ј triphosphate linkage to the mRNA (Hirzmann et al 1993;Volloch et al 1995;Mules et al 1998a). The L1 sequence starts with a run of a variable number G residues, which I propose has accumulated through multiple rounds of cap reverse transcription.…”

Section: Figurementioning

confidence: 99%

The Unusual Phylogenetic Distribution of Retrotransposons: A Hypothesis

Boeke¹

2003

Genome Res.

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Retrotransposons have proliferated extensively in eukaryotic lineages; the genomes of many animals and plants comprise 50% or more retrotransposon sequences by weight. There are several persuasive arguments that the enzymatic lynchpin of retrotransposon replication, reverse transcriptase (RT), is an ancient enzyme. Moreover, the direct progenitors of retrotransposons are thought to be mobile self-splicing introns that actively propagate themselves via reverse transcription, the group II introns, also known as retrointrons. Retrointrons are represented in modern genomes in very modest numbers, and thus far, only in certain eubacterial and organellar genomes. Archaeal genomes are nearly devoid of RT in any form. In this study, I propose a model to explain this unusual distribution, and rationalize it with the proposed ancient origin of the RT gene. A cap and tail hypothesis is proposed. By this hypothesis, the specialized terminal structures of eukaryotic mRNA provide the ideal molecular environment for the lengthening, evolution, and subsequent massive expansion of highly mobile retrotransposons, leading directly to the retrotransposon-cluttered structure that typifies modern metazoan genomes and the eventual emergence of retroviruses.

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Transcription of the 5′-Terminal Cap Nucleotide by RNA-Dependent DNA Polymerase: Possible Involvement in Retroviral Reverse Transcription

Cited by 19 publications

References 15 publications

The human L1 promoter: Variable transcription initiation sites and a major impact of upstream flanking sequence on promoter activity

The human L1 promoter: Variable transcription initiation sites and a major impact of upstream flanking sequence on promoter activity

End-to-End Template Jumping by the Reverse Transcriptase Encoded by the R2 Retrotransposon

The Unusual Phylogenetic Distribution of Retrotransposons: A Hypothesis

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