A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing.
Cell Rep
; 12(4): 562-72, 2015 Jul 28.
Article
em En
| MEDLINE
| ID: mdl-26190105
ABSTRACT
X-chromosome inactivation is the process that evolved in mammals to equalize levels of X-linked gene expression in XX females relative to XY males. Silencing of a single X chromosome in female cells is mediated by the non-coding RNA Xist. Although progress has been made toward identifying factors that function in the maintenance of X inactivation, the primary silencing factors are largely undefined. We developed an shRNA screening strategy to produce a ranked list of candidate primary silencing factors. Validation experiments performed on several of the top hits identified the SPOC domain RNA binding proteins Rbm15 and Spen and Wtap, a component of the m6A RNA methyltransferase complex, as playing an important role in the establishment of Xist-mediated silencing. Localization analysis using super-resolution 3D-SIM microscopy demonstrates that these factors co-localize with Xist RNA within the nuclear matrix subcompartment, consistent with a direct interaction.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Proteínas de Transporte
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Proteínas de Ligação a RNA
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Inativação Gênica
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Proteínas de Ligação a DNA
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Células-Tronco Embrionárias
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RNA Longo não Codificante
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido