Mobile elements and disease

Current Opinion in Genetics and Development

Volumn 8, Issue 3, 1998, Pages 343-350

  Kazazian Jr , Haig H ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GENETIC DISORDER; GENOME; HUMAN; LONG TERMINAL REPEAT; MAMMAL; NONHUMAN; PRIORITY JOURNAL; RETROPOSON; REVIEW; TRANSPOSON;

EID: 0032102720     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(98)80092-0     Document Type: Article

References (65)

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44. Moran JV, Holmes SE, Naas TP, DeBerardinis RJ, Boeke JD, Kazazian HH. High frequency retrotransposition in cultured mammalian cells. of outstanding interest Cell. 87:1996;917-927 The authors report an efficient assay for retrotransposition of human L1 elements in HeLa cells. L1 progenitors of disease-producing insertions (L1.2 and LRE2) retrotransposed autonomously into various chromosomal locations at high frequency from an episome. The high frequency of events detected by the assay (1 event in 500-1000 cells) allowed analysis of point mutations in conserved domains of L1.2. These mutations demonstrated that ORF1 and the reverse transcriptase domain of ORF2 are critical for retrotransposition.
45. Sassaman DM, Dombroski BA, Moran JV, Kimberland ML, Naas TP, DeBeradinis RJ, Gabriel A, Swergold GD, Kazazian HH Jr. Many human L1 elements are capable of retrotransposition. of outstanding interest Nat Genet. 16:1997;37-43 The authors selectively screened for full-length Ta subset L1 elements because the bulk of new L1 insertions in humans are derived from the Ta subset. Four of 13 Ta elements isolated were able to retrotranspose in HeLa cells. Two other L1s from the subfamily of a previously-isolated active element also retrotransposed at very high frequencies which were roughly 5-10 times those of L1.2 and LRE2 [44]. Based on the total number of full-length Ta subset L1s in the genome and the fraction of these L1s that are active, the authors estimated that 30-60 retrotranspositionally-competent L1s exist in the diploid human genome.
46. F, related to an ancient subfamily, F. These L1s retained the capacity to retrotranspose at high frequency in cultured cells. As this subfamily has many full-length members, the authors suggest that many mouse L1s may be active.
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59. Eickbush TH. Telomerase and retrotransposons: which came first? of outstanding interest Science. 277:1997;911-912 The author used an alternative rooting of the phylogenetic tree of retroelements, which does not require transfer of sequences from eukaryotes to prokaryotes, from that of [58]. This rooting provided evidence that telomerases arose from non-LTR retrotransposons, suggesting that retrotransposons were recruited in early eukaryotes to supply a critical function to the cell. The data suggest another way in which retrotransposons have shaped eukaryotic genomes.
60. of special interest Dhellin O, Maestre J, Heidmann T. Functional difference between the human LINE retrotransposon and retroviral reverse transcriptases for in vivo mRNA reverse transcriptase. of special interest EMBO J. 16:1997;6590-6602 The authors assayed the RT activity of an active human L1 and that of two retroviruses. Moloney murine leukemia virus and human HIV, in HeLa cells. They delineated the functional RT domain within the L1 element and showed that it had high efficiency and activity with no sequence specificity. In contrast, retroviral RTs showed no activity in the assay. Strikingly, the authors also detected synthesis of cDNAs derived from endogenous mRNAs by L1, but not retroviral RT. The study suggests, but does not prove, that L1 RT may be involved in processed pseudogene formation. The data also suggest that L1 RT may have two possible modes of action. TPRT in the nucleus and reverse transcription of poly A RNAs in the cytoplasm.
61. Boeke JD. LINEs and Alus - the polyA connection. of special interest Nat Genet. 16:1997;6-7 The author attempts to answer the question, if L1 proteins have a cis preference, how can they provide the machinery for Alu retrotransposition? He hypothesizes that Alu RNA ends up on the ribosomal subunit close to L1 RNA because of its complex with SRP9/14. Furthermore, as L1 RT does not appear to require a specific interacting sequence on the RNA, he proposes that the poly A tail which is common to L1 RNA, Alu RNA, and cellular mRNA is a binding site for L1 RT. Although the latter proposal has been discussed previously, the proposed mechanism for Alu retrotransposition is novel and plausible.
62. Sarrowa J, Chang DY, Maraia RJ. The decline in human Alu retroposition was accompanied by an asymmetric decrease in SRP9/14 binding to dimeric Alu RNA and increased expression of small cytoplasmic Alu RNA. Mol Cell Biol. 17:1997;1144-1151.
63. Jurka J. Sequence patterns indicate an enzymatic involvement in integration of mammalian retroposons. of outstanding interest Proc Natl Acad Sci USA. 94:1997;1872-1877 Jurka analyzed the integration sites for a large number of Alu elements and a small number of L1 elements and processed pseudogenes. He found a consensus integration site sequence for all of these elements consisting of 5′-TT/AAAA where / denotes the nick site. As the consensus sequence is similar to that observed for a larger number of L1 insertions in vivo and in HeLa cells [56], he proposes that L1 endonuclease mediates integration not only of L1 elements but also of Alu elements and processed pseudogenes.
64. of special interest Luan DD, Eickbush TH. RNA template requirements for target DNA-primed reverse transcription by the R2 retrotransposable element. Mol Cell Biol. 15:1995;3882-3891.
65. Kazazian HH Jr, Moran JV. The impact of L1 retrotransposons on the human genome. Nat Genet. 19:1998;19-24.