Nucleoside Analogue Reverse Transcriptase Inhibitors Differentially Inhibit Human LINE-1 Retrotransposition
SMC Affiliated Work
1
Status
Faculty
School
School of Science
Department
Biology
Document Type
Article
Publication Date
2-2008
Publication / Conference / Sponsorship
PLoS One
Description/Abstract
Background
Intact LINE-1 elements are the only retrotransposons encoded by the human genome known to be capable of autonomous replication. Numerous cases of genetic disease have been traced to gene disruptions caused by LINE-1 retrotransposition events in germ-line cells. In addition, genomic instability resulting from LINE-1 retrotransposition in somatic cells has been proposed as a contributing factor to oncogenesis and to cancer progression. LINE-1 element activity may also play a role in normal physiology.
Methods and Principal Findings
Using an in vitro LINE-1 retrotransposition reporter assay, we evaluated the abilities of several antiretroviral compounds to inhibit LINE-1 retrotransposition. The nucleoside analogue reverse transcriptase inhibitors (nRTIs): stavudine, zidovudine, tenofovir disoproxil fumarate, and lamivudine all inhibited LINE-1 retrotransposition with varying degrees of potencies, while the non-nucleoside HIV-1 reverse transcriptase inhibitor nevirapine showed no effect.
Conclusions/Significance
Our data demonstrates the ability for nRTIs to suppress LINE-1 retrotransposition. This is immediately applicable to studies aimed at examining potential roles for LINE-1 retrotransposition in physiological processes. In addition, our data raises novel safety considerations for nRTIs based on their potential to disrupt physiological processes involving LINE-1 retrotransposition.
Keywords
HIV-1, Human genomics, Physiological processes, Reverse transcription, Enzyme inhibitors, Reverse transcriptase inhibitors, Gene disruption, Nucleosides
Scholarly
yes
Peer Reviewed
1
DOI
10.1371/journal.pone.0001547
Volume
3
Issue
2
First Page
e1547
Disciplines
Biology
Rights
Open Access journal
Original Citation
Jones RB, Garrison KE, Wong JC, Duan EH, Nixon DF, Ostrowski MA. 2008. Nucleoside Analogue Reverse Transcriptase Inhibitors Differentially Inhibit Human LINE-1 Retrotransposition. PLoS One 3 (2): e1547. https://doi.org/10.1371/journal.pone.0001547
Repository Citation
Jones, R. Brad; Garrison, Keith; Wong, Jessica; Duan, Erick; Nixon, Douglas; and Ostrowski, Mario. Nucleoside Analogue Reverse Transcriptase Inhibitors Differentially Inhibit Human LINE-1 Retrotransposition (2008). PLoS One. 3 (2), e1547 10.1371/journal.pone.0001547 [article]. https://digitalcommons.stmarys-ca.edu/school-science-faculty-works/254
