A potential role for RNA interference in controlling the activity of the human LINE-1 retrotransposon

被引:75
|
作者
Soifer, HS
Zaragoza, A
Peyvan, M
Behlke, MA
Rossi, JJ
机构
[1] City Hope Natl Med Ctr, Div Mol Biol, Duarte, CA 91010 USA
[2] City Hope Natl Med Ctr, Grad Sch Biol Sci, Beckman Res Inst, Duarte, CA 91010 USA
[3] Integrated DNA Technol Inc, Div Mol Genet, Coralville, IA 53341 USA
关键词
D O I
10.1093/nar/gki223
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Long interspersed nuclear elements (LINE-1 or L1) comprise 17% of the human genome, although only 80-100 L1s are considered retrotransposition-competent (RC-L1). Despite their small number, RC-L1s are still potential hazards to genome integrity through insertional mutagenesis, unequal recombination and chromosome rearrangements. In this study, we provide several lines of evidence that the LINE-1 retrotransposon is susceptible to RNA interference (RNAi). First, double-stranded RNA (dsRNA) generated in vitro from an L1 template is converted into functional short interfering RNA (siRNA) by DICER, the RNase III enzyme that initiates RNAi in human cells. Second, pooled siRNA from in vitro cleavage of L1 dsRNA, as well as synthetic L1 siRNA, targeting the 5'-UTR leads to sequence-specific mRNA degradation of an L1 fusion transcript. Finally, both synthetic and pooled siRNA suppressed retrotransposition from a highly active RC-L1 clone in cell culture assay. Our report is the first to demonstrate that a human transposable element is subjected to RNAi.
引用
收藏
页码:846 / 856
页数:11
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