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L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells

Nature Structural & Molecular Biology volume 13, pages 763–771 (2006)Cite this article

Abstract

LINE-1s, or L1s, are highly abundant retrotransposons comprising 17% of the human genome. Most L1s are retrotransposition defective; nonetheless, there are ∼100 full-length L1s potentially capable of retrotransposition in the diploid genome. L1 retrotransposition may be detrimental to the host and thus needs to be controlled. Previous studies have identified sense and antisense promoters in the 5′ UTR of full-length human L1. Here we show that the resulting bidirectional transcripts can be processed to small interfering RNAs (siRNAs) that suppress retrotransposition by an RNA interference (RNAi) mechanism. We thus provide evidence that RNAi triggered by antisense transcripts may modulate human L1 retrotransposition efficiently and economically. L1-specific siRNAs are among the first natural siRNAs reported in mammalian systems. This work may contribute to understanding the regulatory role of abundant antisense transcripts in eukaryotic genomes.

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Figure 1: Characterization of the ASP in the human L1 5′ UTR.
Figure 2: Bidirectional transcripts of 5′ UTR generate L1-specific siRNAs.
Figure 3: ASP encodes an inhibitory effect on L1 retrotransposition.
Figure 4: ASP induces the mRNA degradation of 5′ UTR–derived transcripts.
Figure 5: RNAi is an intrinsic mechanism for human L1 retrotransposon silencing.

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Acknowledgements

We thank Z. Mourelatos, P. Sniegowski, S. Liebhaber and J. Mayer for helpful discussion and technical advice and D. Babushok and J. Goodier for critical reading of the manuscript. This work was supported by US National Institutes of Health grant GM 045398.

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  1. Department of Genetics, University of Pennsylvania School of Medicine, Rm. 475 Clinical Research Building, 415 Curie Boulevard, Philadelphia, 19104, Pennsylvania, USA

    Nuo Yang & Haig H Kazazian Jr.

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N.Y. contributed to the concept, performed the experiments, analyzed the data and wrote the manuscript. H.H.K. contributed to the concept, analyzed the data and revised the manuscript.

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Correspondence to Haig H Kazazian Jr..

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Yang, N., Kazazian, H. L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells. Nat Struct Mol Biol 13, 763–771 (2006). https://doi.org/10.1038/nsmb1141

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