DNA makes RNA makes protein. The second step of that pathway - the critical function of RNA in genetic information transfer - is exquisitely regulated. mRNA activity, stability and location are controlled by factors that recognize specific RNA sequences. The PUF proteins are a widespread family of mRNA regulatory proteins that control key steps in early development and are required for establishing memory. They must find and recognize specific mRNAs, and then execute that mRNA's fate - activation, repression, destruction, or movement. We elucidate the way in which these proteins form networks of control - recognizing and controlling a substantial proportion of the mRNAs in human cells. They act through collaborations with protein partners - interactions that are conserved from yeast to humans. PUF proteins and their partners have important roles in development, homeostasis, cellular senescence, and human fertility. The networks of RNAs they control are vital in these processes.

Public Health Relevance

The proposed work will illuminate how a widespread family of mRNA regulatory proteins work. These proteins and their protein partners control stem cells and participate in the formation of memory. Understanding how they work is likely to provide practical opportunities for diagnosis and intervention of a range of clinical conditions.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Molecular Genetics B Study Section (MGB)
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Bender, Michael T
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University of Wisconsin Madison
Schools of Earth Sciences/Natur
United States
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Campbell, Zachary T; Valley, Cary T; Wickens, Marvin (2014) A protein-RNA specificity code enables targeted activation of an endogenous human transcript. Nat Struct Mol Biol 21:732-8
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Koh, Yvonne Y; Wickens, Marvin (2014) Identifying proteins that bind a known RNA sequence using the yeast three-hybrid system. Methods Enzymol 539:195-214
Koh, Yvonne Y; Wickens, Marvin (2014) Determining the RNA specificity and targets of RNA-binding proteins using a three-hybrid system. Methods Enzymol 539:163-81
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