Developmentally regulated piRNA clusters implicate MILI in transposon control.
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.
Aravin
Alexei A
AA
Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Howard Hughes Medical Institute (HHMI), 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Sachidanandam
Ravi
R
Girard
Angelique
A
Fejes-Toth
Katalin
K
Hannon
Gregory J
GJ
D020413:3' Untranslated Regions; D000818:Animals; D060565:Argonaute Proteins; D016000:Cluster Analysis; D019295:Computational Biology; D019175:DNA Methylation; D007426:Genes, Intracisternal A-Particle; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008540:Meiosis; D051379:Mice; D009154:Mutation; D011506:Proteins / Q000378:metabolism*; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D018626:Retroelements; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020086:Short Interspersed Nucleotide Elements; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism*; D013091:Spermatogenesis; D013489:Suppression, Genetic
D020413:3' Untranslated Regions; D060565:Argonaute Proteins; C448521:Piwil2 protein, mouse; D011506:Proteins; D016372:RNA, Antisense; D022661:RNA, Untranslated; D018626:Retroelements