Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile.
Nat Struct Mol Biol
; 16(6): 639-46, 2009 Jun.
Article
em En
| MEDLINE
| ID: mdl-19465913
ABSTRACT
Piwi proteins and their associated Piwi-interacting RNAs (piRNAs) are implicated in transposon silencing in the mouse germ line. There is currently little information on additional proteins in the murine Piwi complex and how they might regulate the entry of transcripts that accumulate as piRNAs in the Piwi ribonucleoprotein (piRNP). We isolated Mili-containing complexes from adult mouse testes and identified Tudor domain-containing protein-1 (Tdrd1) as a factor specifically associated with the Mili piRNP throughout spermatogenesis. Complex formation is promoted by the recognition of symmetrically dimethylated arginines at the N terminus of Mili by the tudor domains of Tdrd1. Similar to a Mili mutant, mice lacking Tdrd1 show derepression of L1 transposons accompanied by a loss of DNA methylation at their regulatory elements and delocalization of Miwi2 from the nucleus to the cytoplasm. Finally, we show that Mili piRNPs devoid of Tdrd1 accept the entry of abundant cellular transcripts into the piRNA pathway and accumulate piRNAs with a profile that is drastically different from that of the wild type. Our data suggest that Tdrd1 ensures the entry of correct transcripts into the normal piRNA pool.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Elementos de DNA Transponíveis
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Proteínas
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Ribonucleoproteínas Nucleares Pequenas
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RNA Interferente Pequeno
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article