Département de Biologie

École normale supérieure

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Séminaires du Département de Biologie

  • lundi 3 novembre 2014 de 11:00 à 12:30
    Salle Favard
    Gilles Laurent
    Max Planck Institute for Brain Research,
    Invité(e) par : Pierre PAOLETTI - Section NEUROSCIENCES et German SUMBRE - Section NEUROSCIENCES
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  • RNA interference (RNAi) is largely known as a negative regulator of gene expression. The mechanisms by which RNAi negatively regulate gene expression include Argonaute proteins and their small RNA cofactors short interfering RNAs (siRNAs) inhibiting mRNA translation, mRNA or pre-mRNA degradation, and RNA transcription. Interestingly, the association of nuclear Argonaute proteins with transcriptionally active gene loci has been described in animals, including humans, raising the interesting possibility that RNAi-mediated mechanism could regulate active genes. I will present the results of my work on the C. elegans nuclear Argonaute protein CSR-1. CSR-1 is exclusively loaded with endogenous siRNAs (endo-siRNAs) antisense to thousands of active germline transcripts. CSR-1 associates with chromatin, and inactivation of the components of the CSR-1 pathway leads to sterility, embryonic lethality, and chromosome organization defects. To investigate the nuclear role of CSR-1, I adapted the Global Run-On sequencing (GRO-seq) method, which measures nascent RNA polymerase II (Pol II) transcripts in a genome-wide fashion, for use in C. elegans. Surprisingly, I discovered that CSR-1 and its associated endo-siRNAs globally promote sense-oriented Pol II transcription of germline genes. Moreover, CSR-1 directly interacts with nascent RNA target transcripts and the Pol II machinery in siRNA-dependent manner. Loss of CSR-1 function results in global increase in antisense transcription and ectopic transcription of silent chromatin domains, which affects centromere formation and chromatin organization. Together, these results suggest that the CSR-1 pathway has a role in maintaining the genome-wide distribution of Pol II and thus propagating the distinction between active and silent chromatin domains. I propose a model where CSR-1 endo-siRNAs may constitute an RNA-based system for propagating the memory of actively transcribed genomic hromatin regions across generations.
    mardi 4 novembre 2014 de 14:00 à 15:30
    Salle Favard
    Germano Cecere
    Columbia University Medical Center, New York,
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Département de Biologie
École Normale Supérieure
46, Rue d’Ulm
75005 Paris
Directeur :
Antoine Triller
Directeur ajdoint :
Patrick Charnay
Secrétariat du département :
Virginie Bues
Secrétariat de l’enseignement :
Anne Zalmanski