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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050942-18
Application #
8604714
Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Bender, Michael T
Project Start
1994-04-01
Project End
2016-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
18
Fiscal Year
2014
Total Cost
$419,853
Indirect Cost
$133,150
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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
Koh, Yvonne Y; Wickens, Marvin (2014) Dissecting a known RNA-protein interaction using a yeast three-hybrid system. Methods Enzymol 539:183-93
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
Ellery, Paul E R; Maroney, Susan A; Martinez, Nicholas D et al. (2014) Translation of human tissue factor pathway inhibitor-* mRNA is controlled by alternative splicing within the 5' untranslated region. Arterioscler Thromb Vasc Biol 34:187-95
Menichelli, Elena; Wu, Joann; Campbell, Zachary T et al. (2013) Biochemical characterization of the Caenorhabditis elegans FBF.CPB-1 translational regulation complex identifies conserved protein interaction hotspots. J Mol Biol 425:725-37
Lapointe, Christopher P; Wickens, Marvin (2013) The nucleic acid-binding domain and translational repression activity of a Xenopus terminal uridylyl transferase. J Biol Chem 288:20723-33
Wu, Joann; Campbell, Zachary T; Menichelli, Elena et al. (2013) A protein.protein interaction platform involved in recruitment of GLD-3 to the FBF.fem-3 mRNA complex. J Mol Biol 425:738-54
Zhang, Yan; Cooke, Amy; Park, Sookhee et al. (2013) Bicaudal-C spatially controls translation of vertebrate maternal mRNAs. RNA 19:1575-82
LeGendre, Jacqueline Baca; Campbell, Zachary T; Kroll-Conner, Peggy et al. (2013) RNA targets and specificity of Staufen, a double-stranded RNA-binding protein in Caenorhabditis elegans. J Biol Chem 288:2532-45

Showing the most recent 10 out of 37 publications