Developmentally regulated piRNA clusters implicate MILI in transposon control

Alexei A. Aravin, Ravi Sachidanandam, Angelique Girard, Katalin Fejes-Toth, Gregory J. Hannon

Research output: Contribution to journalArticlepeer-review

751 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)744-747
Number of pages4
JournalScience
Volume316
Issue number5825
DOIs
StatePublished - 4 May 2007
Externally publishedYes

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