PT - JOURNAL ARTICLE AU - Aravin, Alexei A. AU - Sachidanandam, Ravi AU - Girard, Angelique AU - Fejes-Toth, Katalin AU - Hannon, Gregory J. TI - Developmentally Regulated piRNA Clusters Implicate MILI in Transposon Control AID - 10.1126/science.1142612 DP - 2007 May 04 TA - Science PG - 744--747 VI - 316 IP - 5825 4099 - http://science.sciencemag.org/content/316/5825/744.short 4100 - http://science.sciencemag.org/content/316/5825/744.full SO - Science2007 May 04; 316 AB - Nearly half of the mammalian genome is composed of repeated sequences. In Drosophila, Piwi proteins exert control over transposons. However, mammalian Piwi proteins, MIWI and MILI, partner with Piwi-interacting RNAs (piRNAs) that are depleted of repeat sequences, which raises questions about a role for mammalian Piwi's in transposon control. A search for murine small RNAs that might program Piwi proteins for transposon suppression revealed developmentally regulated piRNA loci, some of which resemble transposon master control loci of Drosophila. We also find evidence of an adaptive amplification loop in which MILI catalyzes the formation of piRNA 5′ ends. Mili mutants derepress LINE-1 (L1) and intracisternal A particle and lose DNA methylation of L1 elements, demonstrating an evolutionarily conserved role for PIWI proteins in transposon suppression.