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.
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.
| Lapointe, Christopher P; Stefely, Jonathan A; Jochem, Adam et al. (2018) Multi-omics Reveal Specific Targets of the RNA-Binding Protein Puf3p and Its Orchestration of Mitochondrial Biogenesis. Cell Syst 6:125-135.e6 |
| Aoki, Scott T; Porter, Douglas F; Prasad, Aman et al. (2018) An RNA-Binding Multimer Specifies Nematode Sperm Fate. Cell Rep 23:3769-3775 |
| Lapointe, Christopher P; Wickens, Marvin (2018) RNA Tagging: Preparation of High-Throughput Sequencing Libraries. Methods Mol Biol 1649:455-471 |
| Wilinski, Daniel; Buter, Natascha; Klocko, Andrew D et al. (2017) Recurrent rewiring and emergence of RNA regulatory networks. Proc Natl Acad Sci U S A 114:E2816-E2825 |
| Lapointe, Christopher P; Preston, Melanie A; Wilinski, Daniel et al. (2017) Architecture and dynamics of overlapped RNA regulatory networks. RNA 23:1636-1647 |
| Shin, Heaji; Haupt, Kimberly A; Kershner, Aaron M et al. (2017) SYGL-1 and LST-1 link niche signaling to PUF RNA repression for stem cell maintenance in Caenorhabditis elegans. PLoS Genet 13:e1007121 |
| Prasad, Aman; Porter, Douglas F; Kroll-Conner, Peggy L et al. (2016) The PUF binding landscape in metazoan germ cells. RNA 22:1026-43 |
| 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 |
| Campbell, Zachary T; Wickens, Marvin (2015) Probing RNA-protein networks: biochemistry meets genomics. Trends Biochem Sci 40:157-64 |
| 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 |
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