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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 May 2015

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 …


Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman Dec 2012

Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman

Dr Robert Brown

Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct …