Group II intron mobility occurs by target DNA-primed reverse transcription

Zimmerly, Steven; Guo, Haixun; Perlman, Philip S.; Lambowitz, Alan M.

doi:10.1016/0092-8674(95)90027-6

Cited by 258 publications

(193 citation statements)

References 27 publications

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“…We and others have postulated that the most likely origin of the non-LTR elements are the group-II introns found in eubacteria and the organelles of fungi and plants (Zimmerly et al 1995;Cousineau et al 1998;Lambowitz et al 1999). This model is based on both the phylogenetic relationship of their RT domains ) and the similarity of their target primed reverse transcription mechanisms used for insertion (Luan et al 1993;Zimmerly et al 1995). When the Kanaya et al 1996).…”

Section: Non-ltr Retrotransposons Arose Earlier Than Ltr Retrotranspomentioning

confidence: 99%

Phylogenetic Analysis of Ribonuclease H Domains Suggests a Late, Chimeric Origin of LTR Retrotransposable Elements and Retroviruses

Malik¹,

Eickbush²

2001

Genome Res.

214

200

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We have conducted a phylogenetic analysis of the Ribonuclease HI (RNH) domains present in Eubacteria, Eukarya, all long-term repeat (LTR)-bearing retrotransposons, and several late-branching clades of non-LTR retrotransposons. Analysis of this simple yet highly conserved enzymatic domain from these disparate sources provides surprising insights into the evolution of eukaryotic retrotransposons. First, it indicates that the lineage of elements leading to vertebrate retroviruses acquired a new RNH domain either from non-LTR retrotransposons or from a eukaryotic host genome. The preexisting retroviral RNH domain degenerated to become the tether (connection) domain of the reverse transcriptase (RT)-RNH complex. Second, it indicates that all LTR retrotransposons arose in eukaryotes well after the origin of the non-LTR retrotransposons. Because of the younger age of the LTR retrotransposons, their complex structure, and the absence of any prokaryotic precursors, we propose that the LTR retrotransposons originated as a fusion between a DNA-mediated transposon and a non-LTR retrotransposon. The resulting two-step mechanism of LTR retrotransposition, in which RNA is reverse transcribed away from the chromosomal target site, rather than directly onto the target site, was probably an adaptation to the uncoupling of transcription and translation in eukaryotic cells.

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Section: Non-ltr Retrotransposons Arose Earlier Than Ltr Retrotranspomentioning

confidence: 99%

Phylogenetic Analysis of Ribonuclease H Domains Suggests a Late, Chimeric Origin of LTR Retrotransposable Elements and Retroviruses

Malik¹,

Eickbush²

2001

Genome Res.

214

200

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“…While recent biochemical analyses have revealed novel priming mechanisms associated with several nonretroviral RTs (22)(23)(24)(25)(26), no study has addressed the rate or spectrum of errors occurring during a cycle of nonretroviral retrotransposition. Such studies are impeded by the polymorphic nature of multicopy elements in the genome (27,28), their variable expression, and the difficulty of identifying events resulting from single rounds of replication.…”

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confidence: 99%

Replication infidelity during a single cycle of Ty1 retrotransposition.

Gabriel

Willems

Mules

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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Retroviruses undergo a high frequency of genetic alterations during the process of copying their RNA genomes. However, little is known about the replication fidelity of other elements that transpose via reverse transcription of an RNA intermediate. The complete sequence of 29 independently integrated copies of the yeast retrotransposon Tyl (173,043 nt) was determined, and the mutation rate during a single cycle of replication was calculated. The observed base substitution rate of 2.5 x 10-5 bp per replication cycle suggests that this intracellular element can mutate as rapidly as retroviruses. The pattern and distribution of errors in the Tyl genome is nonrandom and provides clues to potential in vivo molecular mechanisms of reverse transcriptase-mediated error generation, including heterogeneous RNase H cleavage of Tyl RNA, addition of terminal nontemplated bases, and transient dislocation and realignment of primer-templates.Overall, analysis of errors generated during Tyl replication underscores the utility of a genetically tractable model system for the study of reverse transcriptase fidelity.Reverse transcription is a notoriously error-prone process. Mutations occurring during retroviral replication include simple base substitutions and frameshifts as well as complex deletions, deletions with insertions, and hypermutations (1-6).This low fidelity of replication is presumed to be the basis for the rapid genome evolution of retroviruses as well as for the ability of human immunodeficiency virus to evade its host immune system and develop drug resistance. Biochemical studies using purified retroviral reverse transcriptases (RTs) have elucidated multiple potential error-generating mechanisms, including extension past mismatched bases (7-11), poor discrimination of dNTPs (12-14), lack of associated 3' to 5' exonuclease activities (9, 15), slippage of primer-templates (16,17), and addition of nontemplated bases at the ends of template strands (18,19).Retroviruses are the most highly visible members of a ubiquitous and varied confederation of genetic elements linked by their capacity to replicate by reverse transcription of an RNA intermediate (20,21). While recent biochemical analyses have revealed novel priming mechanisms associated with several nonretroviral , no study has addressed the rate or spectrum of errors occurring during a cycle of nonretroviral retrotransposition. Such studies are impeded by the polymorphic nature of multicopy elements in the genome (27, 28), their variable expression, and the difficulty of identifying events resulting from single rounds of replication. However, these problems could be obviated using a model system where transposition is limited to a single, marked element, where expression of the multiple endogenous copies is repressed, and where transposition events are trapped and prevented from secondary replication. The retrotransposon Tyl, from the yeast Saccharomyces cerevisiae, provides just such a system.Tyl is one of the most intensively studied retrotransposons. Its ...

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“…PLEs are the only retrotransposons known to contain a Uri EN domain, and here we show that in the case of Penelope it exhibits EN activity and requires amino acids corresponding to the most conserved residues in GIY-YIG proteins. This activity could cleave the target DNA to initiate reverse transcription and integration by a mechanism similar to that used by R2Bm, L1, and probably other non-LTR retrotransposons (27)(28)(29), as well as group II introns (30), arguing in favor of the ancestral nature of this mechanism.…”

Section: Discussionmentioning

confidence: 99%

Reverse transcriptase and endonuclease activities encoded by Penelope -like retroelements

Pyatkov

Arkhipova

Malkova

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Penelope-like elements are a class of retroelement that have now been identified in >50 species belonging to at least 10 animal phyla. The Penelope element isolated from Drosophila virilis is the only transpositionally active representative of this class isolated so far. The single ORF of Penelope and its relatives contains regions homologous to a reverse transcriptase of atypical structure and to the GIY-YIG, or Uri, an endonuclease (EN) domain not previously found in retroelements. We have expressed the single ORF of Penelope in a baculovirus expression system and have shown that it encodes a polyprotein with reverse transcriptase activity that requires divalent cations (Mn 2؉ and Mg 2؉ ). We have also expressed and purified the EN domain in Escherichia coli and have demonstrated that it has EN activity in vitro. Mutations in the conserved residues of the EN catalytic module abolish its nicking activity, whereas the DNA-binding properties of the mutant proteins remain unaffected. Only one strand of the target sequence is cleaved, and there is a certain degree of cleavage specificity. We propose that the Penelope EN cleaves the target DNA during transposition, generating a primer for reverse transcription. Our results show that an active Uri EN has been adopted by a retrotransposon.GIY-YIG endonuclease ͉ retrotransposons ͉ Drosophila virilis ͉ Uri domain

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Group II intron mobility occurs by target DNA-primed reverse transcription

Cited by 258 publications

References 27 publications

Phylogenetic Analysis of Ribonuclease H Domains Suggests a Late, Chimeric Origin of LTR Retrotransposable Elements and Retroviruses

Phylogenetic Analysis of Ribonuclease H Domains Suggests a Late, Chimeric Origin of LTR Retrotransposable Elements and Retroviruses

Replication infidelity during a single cycle of Ty1 retrotransposition.

Reverse transcriptase and endonuclease activities encoded by Penelope -like retroelements

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