- 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. We focus on the PUF proteins, a widespread family of mRNA regulatory proteins that control key steps in early development and are required for establishing memory. We propose to determine how these proteins find and recognize specific mRNAs, and how they then execute that decision.

Public Health Relevance

Project Narrative The proposed work will illuminate how a widespread family of mRNA regulatory proteins work. These proteins control stem cells and participate in the formation of memory. Understanding how they work should provide practical opportunities for intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050942-16
Application #
8197924
Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Bender, Michael T
Project Start
1994-04-01
Project End
2013-01-13
Budget Start
2011-12-01
Budget End
2013-01-13
Support Year
16
Fiscal Year
2012
Total Cost
$342,006
Indirect Cost
$106,782
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
Aoki, Scott T; Kershner, Aaron M; Bingman, Craig A et al. (2016) PGL germ granule assembly protein is a base-specific, single-stranded RNase. Proc Natl Acad Sci U S A 113:1279-84
Prasad, Aman; Porter, Douglas F; Kroll-Conner, Peggy L et al. (2016) The PUF binding landscape in metazoan germ cells. RNA 22:1026-43
Campbell, Zachary T; Wickens, Marvin (2015) Probing RNA-protein networks: biochemistry meets genomics. Trends Biochem Sci 40:157-64
Wilinski, Daniel; Qiu, Chen; Lapointe, Christopher P et al. (2015) RNA regulatory networks diversified through curvature of the PUF protein scaffold. Nat Commun 6:8213
Lapointe, Christopher P; Wilinski, Daniel; Saunders, Harriet A J et al. (2015) Protein-RNA networks revealed through covalent RNA marks. Nat Methods 12:1163-70
Porter, Douglas F; Koh, Yvonne Y; VanVeller, Brett et al. (2015) Target selection by natural and redesigned PUF proteins. Proc Natl Acad Sci U S A 112:15868-73
Waghray, Shruti; Williams, Clay; Coon, Joshua J et al. (2015) Xenopus CAF1 requires NOT1-mediated interaction with 4E-T to repress translation in vivo. RNA 21:1335-45
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) 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

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