Transposition of the LINE-like retrotransposon TART to Drosophila chromosome termini.

Sheen, Fang-miin; Levis, Robert

doi:10.1073/pnas.91.26.12510

Cited by 136 publications

(118 citation statements)

References 25 publications

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“…For example, Drosophila lacks a formal telomerase and relies on three retrotransposons (HetA, TART, and TAHRE) to maintain its telomeres (61)(62)(63)(64)(65). Interestingly, TART and TAHRE have an apparent APE domain, suggesting that, unlike ENi L1 retrotransposition, this putative endonuclease may be important for telomere localization (66).…”

Section: Discussionmentioning

confidence: 99%

Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase

Kopera¹,

Moldovan²,

Morrish³

et al. 2011

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

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Long interspersed element-1 (LINE-1 or L1) retrotransposons encode two proteins (ORF1p and ORF2p) that contain activities required for conventional retrotransposition by a mechanism termed target-site primed reverse transcription. Previous experiments in XRCC4 or DNA protein kinase catalytic subunit-deficient CHO cell lines, which are defective for the nonhomologous endjoining DNA repair pathway, revealed an alternative endonuclease-independent (ENi) pathway for L1 retrotransposition. Interestingly, some ENi retrotransposition events in DNA protein kinase catalytic subunit-deficient cells are targeted to dysfunctional telomeres. Here we used an in vitro assay to detect L1 reverse transcriptase activity to demonstrate that wild-type or endonuclease-defective L1 ribonucleoprotein particles can use oligonucleotide adapters that mimic telomeric ends as primers to initiate the reverse transcription of L1 mRNA. Importantly, these ribonucleoprotein particles also contain a nuclease activity that can process the oligonucleotide adapters before the initiation of reverse transcription. Finally, we demonstrate that ORF1p is not strictly required for ENi retrotransposition at dysfunctional telomeres. Thus, these data further highlight similarities between the mechanism of ENi L1 retrotransposition and telomerase.L ong interspersed element-1 sequences (LINE-1s or L1s) are abundant non-long terminal repeat (non-LTR) retrotransposons that constitute approximately one-sixth (i.e., ≈17%) of human nuclear DNA (1). An estimated 80-100 full-length, retrotransposition competent L1s (RC-L1s) are present in a typical diploid human genome, and a small number, termed "hot L1s" exhibit high retrotransposition efficiencies in cultured human cells (2). Human RC-L1s are ≈6 kb (3, 4) and encode two proteins (ORF1p and ORF2p) required for retrotransposition (5). ORF1p is a 40-kDa protein (6) with RNA binding (7-12) and nucleic acid chaperone activities (13-15). ORF2p is a 150-kDa protein (16, 17) with endonuclease (EN) (18,19) and reverse transcriptase (RT) (20, 21) activities.The mobilization of RC-L1s can be mutagenic (22); germ line and, less often, somatic L1 insertions have led to ≈65 sporadic cases of disease in humans (reviewed in ref. 23). ORF1p and/or ORF2p also can act in trans to mobilize short interspersed elements [e.g., Alu (24) and SINE-VNTR-Alu (25) elements], certain noncoding RNAs [e.g., U6 snRNA and small nucleolar RNAs (24, 26-29)], and some cellular mRNAs, which leads to the formation of processed pseudogenes (30-32). In total, these trans retrotransposition events account for at least an additional 10% of human DNA (1). Moreover, several recent studies have further demonstrated that L1-mediated retrotransposition events are responsible for a significant proportion of interindividual genetic variation in the human population (33-39) and may cause intraindividual variation in the mammalian nervous system (40, 41). L1 retrotransposition likely occurs by a mechanism termed target-site primed reverse transcription (TPRT) (42)...

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Section: Discussionmentioning

confidence: 99%

Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase

Kopera¹,

Moldovan²,

Morrish³

et al. 2011

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

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“…29 The analysis of TART elements in different strains allowed the identification of three TART subfamilies. 32 Although HeT-A, TART and TAHRE are capable of healing broken chromosomes, [32][33][34][35][36] they have never been found in euchromatin. However, arrays of telomeric elements, decayed by numerous in/del mutations, have been found in centromeric and pericentromeric heterochromatin.…”

Section: Three Retrotransposons Maintain Telomeres In Drosophila Melamentioning

confidence: 99%

“…[37][38][39][40][41][42][43] TART and TAHRE have the two open reading frames typical of non-LTR retrotransposons; the ORF1 encodes a putative RNA binding protein and the ORF2 encodes a protein with domains related to both reverse transcriptase (RT) and endonuclease. 31,32 Per contra, HeT-A is an atypical element because it lacks ORF2, so the RT for its transposition must be produced in trans. This type of non-autonomous elements has been described in several species.…”

Section: Three Retrotransposons Maintain Telomeres In Drosophila Melamentioning

confidence: 99%

Telomere maintenance in Drosophila: Rapid transposon evolution at chromosome ends

Villasanté

Pablos²,

Méndez-Lago³

et al. 2008

Cell Cycle

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The maintenance of terminal sequences is an important role of the telomere, since it prevents the loss of internal regions that encode essential genes. In most eukaryotes, this is accomplished by the telomerase. However, telomere length can also be maintained by other mechanisms, such as homologous recombination and transposition of telomeric retrotransposons to the chromosome ends. A remarkable situation is the case of Drosophila, where telomerase was lost, and thus telomeres managed to be maintained by occasional retrotransposition of telomeric elements to the receding ends. In the recent analysis of 12 Drosophila genomes, the multiplicity of autonomous and non-autonomous telomere-specific retrotransposons has revealed extensive and rapid evolution of telomeric DNA. The phylogenetic relationship among these telomeric retrotransposons is congruent with the species phylogeny, suggesting that they have been vertically transmitted from a common ancestor. In this review, we also suggest that the formation of a non-canonical DNA structure at Drosophila telomeres could be the way to protect the ends.

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“…The distalmost sequences of Drosophila telomeres consist of retrotransposons from the HeT-A and TART families (Biessmann et al 1990; Levis et al 1993;Sheen and Levis 1994;Mason and Biessmann 1995). These LINE-type retrotransposons insert specifically at the ends of chromosomes to replenish sequences that are lost because of incomplete DNA replication there.…”

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confidence: 99%

Impairment of Cytotype Regulation of P-Element Activity in Drosophila melanogaster by Mutations in the Su(var)205 Gene

et al. 2005

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Cytotype regulation of transposable P elements in the germ line of Drosophila melanogaster is associated with maternal transmission of P elements inserted at the left telomere of the X chromosome. This regulation is impaired in long-term stocks heterozygous for mutations in Suppressor of variegation 205 [Su(var)205], a gene implicated in the control of telomere length. Regulation by TP5, a structurally incomplete P element at the X telomere, is more profoundly impaired than regulation by TP6, a different incomplete P element inserted at the same site in a TAS repeat at the X telomere. Genetic analysis with the TP5 element indicates that its regulatory ability is not impaired in flies whose fathers came directly from a stock heterozygous for a Su(var)205 mutation, even when the flies themselves carry this mutation. However, it is impaired in flies whose grandfathers came from such a stock. Furthermore, this impairment occurs even when the Su(var)205 mutation is not present in the flies themselves or in their mothers. The impaired regulatory ability of TP5 persists for at least several generations after TP5 X chromosomes extracted from a long-term mutant Su(var)205 stock are made homozygous in the absence of the Su(var)205 mutation. Impairment of TP5-mediated regulation is therefore not directly dependent on the Su(var)205 mutation. However, it is characteristic of the six mutant Su(var)205 stocks that were tested and may be related to the elongated telomeres that develop in these stocks. Impairment of regulation by TP5 is also seen in a stock derived from Gaiano, a wild-type strain that has elongated telomeres due to a dominant mutation in the Telomere elongation (Tel ) gene. Regulation by TP6 is not impaired in the Gaiano genetic background. The regulatory abilities of the TP5 and TP6 elements are therefore not equally susceptible to the effects of elongated telomeres in the mutant Su(var)205 and Gaiano stocks.T HE transposable P elements of Drosophila melanogaster were discovered through their involvement in a syndrome of germ-line abnormalities called hybrid dysgenesis (Kidwell et al. 1977;Bingham et al. 1982). The traits of this syndrome include sterility due to a failure of the gonads to develop (gonadal dysgenesis, GD), the frequent occurrence of mutations and chromosome rearrangements, recombination in males, and chromosome transmission ratio distortion. These traits are seen when P elements are activated in the germ line-an event that occurs in the hybrid offspring of crosses between males with P elements in their genomes and females without these elements. Hybrid dysgenesis is usually not seen in the offspring of the reciprocal crosses because P elements are repressed by a maternally transmitted condition called the P cytotype, which genetic analyses have shown depends on the P elements themselves (Engels 1979a;Sved 1987).The mechanistic basis of the P cytotype is unknown. For many years it was thought to involve P-encoded polypeptides transmitted through the egg cytoplasm (Engels 1989;Rio 1990;...

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Transposition of the LINE-like retrotransposon TART to Drosophila chromosome termini.

Cited by 136 publications

References 25 publications

Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase

Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase

Telomere maintenance in Drosophila: Rapid transposon evolution at chromosome ends

Impairment of Cytotype Regulation of P-Element Activity in Drosophila melanogaster by Mutations in the Su(var)205 Gene

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