title: Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase.
abstract: 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 end-joining 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.
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109-5618, USA. chongh@umich.edu
authors.forename: Huira C
authors.initials: HC
authors.lastname: Kopera
authors.forename: John B
authors.initials: JB
authors.lastname: Moldovan
authors.forename: Tammy A
authors.initials: TA
authors.lastname: Morrish
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Garcia-Perez
authors.forename: John V
authors.initials: JV
authors.lastname: Moran
mesh_terms: D000818:Animals; D016466:CHO Cells; D020134:Catalytic Domain; D006224:Cricetinae; D003412:Cricetulus; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D016366:Open Reading Frames; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D018626:Retroelements / Q000235:genetics; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000648:ultrastructure
chemical_list: D018626:Retroelements; D012194:RNA-Directed DNA Polymerase; D019098:Telomerase