March 10 2015

12:00 158 Hershey Hall

Jesse Zamudio
Koch Institute of Integrative cancer Research, Massachusetts Institute of Technology

Argonaute-mediated gene regulation in mouse embryonic stem cells


The Argonaute (Ago) proteins of the RNA interference (RNAi) pathway are highly conserved mediators of gene regulation. The importance of RNAi regulation in mammalian systems is evident during development and in oncogenic microRNA-dependent control of cellular proliferation. Recently, microRNA target pool competition and additional regulatory mechanisms, such as Ago-mediated transcriptional control, have also been implicated in disease progression. These findings highlight the need for a systems-level characterization of the mammalian RNAi pathway to fully understand and partition its roles in gene regulation. In this seminar, a quantitative assessment of Ago-mediated regulation will be presented through characterization of the first stable Ago-deficient mammalian cells, stoichiometric measurement of Ago-bound RNAs and identification of Ago protein and DNA interactions in embryonic stem cells. In addition to insight into microRNA regulation, potential roles for Ago beyond canonical microRNA repression will be presented. These studies aim toward a comprehensive understanding of RNAi regulation in normal cell states and the contribution of its dysregulation to malignant transformation.















































































































































































































































































































































































































































































































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