Yang Nuo, Kazazian Haig H
Department of Genetics, University of Pennsylvania School of Medicine, Rm. 475 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Nat Struct Mol Biol. 2006 Sep;13(9):763-71. doi: 10.1038/nsmb1141. Epub 2006 Aug 27.
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.
LINE-1元件，即L1元件，是高度丰富的逆转录转座子，占人类基因组的17%。大多数L1元件存在逆转录缺陷；然而，在二倍体基因组中大约有100个全长L1元件具有逆转录能力。L1逆转录可能对宿主有害，因此需要加以控制。以往的研究已在全长人类L1元件的5'非翻译区（UTR）中鉴定出正义和反义启动子。在此我们表明，所产生的双向转录本可被加工成小干扰RNA（siRNA），通过RNA干扰（RNAi）机制抑制逆转录。因此，我们提供了证据表明，由反义转录本触发的RNAi可能有效且经济地调节人类L1逆转录。L1特异性siRNA是哺乳动物系统中最早报道的天然siRNA之一。这项工作可能有助于理解丰富的反义转录本在真核基因组中的调控作用。
