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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2007-05, Vol.316 (5825), p.744-747
Main Authors: Aravin, Alexei A, Sachidanandam, Ravi, Girard, Angelique, Fejes-Toth, Katalin, Hannon, Gregory J
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Animals
Argonaute Proteins
Biological and medical sciences
Cluster Analysis
Computational Biology
DNA
DNA Methylation
Drosophila
Evolutionary biology
Fundamental and applied biological sciences. Psychology
Gene expression regulation
Genes, Intracisternal A-Particle
Genic rearrangement. Recombination. Transposable element
Genomes
Genomics
Long Interspersed Nucleotide Elements
Male
Mammals
Meiosis
Methylation
Mice
Molecular and cellular biology
Molecular genetics
Mutation
Pachytene stage
Proteins - metabolism
Retroelements
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
RNA
RNA, Antisense - genetics
RNA, Antisense - metabolism
RNA, Untranslated - genetics
RNA, Untranslated - metabolism
Short Interspersed Nucleotide Elements
Spermatocytes - cytology
Spermatocytes - metabolism
Spermatogenesis
Suppression, Genetic
Testes
Transposons
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1142612