L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells.
LINE-1s, or L1s, are highly abundant retrotransposons comprising 17% of the human genome. Most L1s are retrotransposition defective; nonetheless, there are approximately 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.
Yang
Nuo
N
Department of Genetics, University of Pennsylvania School of Medicine, Rm. 475 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Kazazian
Haig H
HH
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D020871:RNA Stability / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D018626:Retroelements / Q000235:genetics*
D020121:5' Untranslated Regions; D034741:RNA, Small Interfering; D018626:Retroelements