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Argonaute Protein Identity And Pairing Geometry Determine Cooperativity In Mammalian Rna Silencing, Jennifer Broderick, William Salomon, Sean Ryder, Neil Aronin, Phillip Zamore
Argonaute Protein Identity And Pairing Geometry Determine Cooperativity In Mammalian Rna Silencing, Jennifer Broderick, William Salomon, Sean Ryder, Neil Aronin, Phillip Zamore
Sean P. Ryder
Small RNAs loaded into Argonaute proteins direct silencing of complementary target mRNAs. It has been proposed that multiple, imperfectly complementary small interfering RNAs or microRNAs, when bound to the 3' untranslated region of a target mRNA, function cooperatively to silence target expression. We report that, in cultured human HeLa cells and mouse embryonic fibroblasts, Argonaute1 (Ago1), Ago3, and Ago4 act cooperatively to silence both perfectly and partially complementary target RNAs bearing multiple small RNA-binding sites. Our data suggest that for Ago1, Ago3, and Ago4, multiple, adjacent small RNA-binding sites facilitate cooperative interactions that stabilize Argonaute binding. In contrast, small RNAs …
Fbf Represses The Cip/Kip Cell-Cycle Inhibitor Cki-2 To Promote Self-Renewal Of Germline Stem Cells In C. Elegans, Irene Kalchhauser, Brian Farley, Sandra Pauli, Sean Ryder, Rafal Ciosk
Fbf Represses The Cip/Kip Cell-Cycle Inhibitor Cki-2 To Promote Self-Renewal Of Germline Stem Cells In C. Elegans, Irene Kalchhauser, Brian Farley, Sandra Pauli, Sean Ryder, Rafal Ciosk
Sean P. Ryder
Although the decision between stem cell self-renewal and differentiation has been linked to cell-cycle modifications, our understanding of cell-cycle regulation in stem cells is very limited. Here, we report that FBF/Pumilio, a conserved RNA-binding protein, promotes self-renewal of germline stem cells by repressing CKI-2(Cip/Kip), a Cyclin E/Cdk2 inhibitor. We have previously shown that repression of CYE-1 (Cyclin E) by another RNA-binding protein, GLD-1/Quaking, promotes germ cell differentiation. Together, these findings suggest that a post-transcriptional regulatory circuit involving FBF and GLD-1 controls the self-renewal versus differentiation decision in the germline by promoting high CYE-1/CDK-2 activity in stem cells, and inhibiting CYE-1/CDK-2 …