The subject of this research project is the structural molecular biology of RNA 3'-end processing and of the integration with transcription and RNA export. RNA processing reactions can be reconstituted in vitro, but they occur more efficiently in the cell because they are closely integrated with transcription. How these biological processes are regulated and integrated with each other remains unclear at the molecular level and poorly understood structurally. Thus, dissecting how transcription and RNA export are coupled with processing at the molecular and structural level, as we propose to do, is an essential step to understanding how gene expression pathways are integrated and regulated. In order to address these biological problems, we propose to study: (1) the molecular basis for the specific recognition of different phosphorylated forms of the C-terminal domain of the RNA polymerase, and how a new phosphatase enzyme generates the form of the CTD found at the 3'-end of genes;(2) the molecular basis for RNA recognition by RNA processing factors in yeast and in vertebrates;(3) the interaction of RNA processing factors with factors that regulate RNA export.

Public Health Relevance

Processing of the 3'-end of RNA by cleavage and polyadenylation is an essential maturation step that is increasingly understood to be critically regulated in cancer and development. Studying structurally and molecularly how it occurs, as we propose, is essential to understanding gene expression and its regulation.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Macromolecular Structure and Function B Study Section (MSFB)
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Preusch, Peter C
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University of Washington
Schools of Medicine
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Nemec, Corey M; Yang, Fan; Gilmore, Joshua M et al. (2017) Different phosphoisoforms of RNA polymerase II engage the Rtt103 termination factor in a structurally analogous manner. Proc Natl Acad Sci U S A 114:E3944-E3953
Yang, Fan; Hsu, Peter; Lee, Susan D et al. (2017) The C terminus of Pcf11 forms a novel zinc-finger structure that plays an essential role in mRNA 3'-end processing. RNA 23:98-107
Borkar, Aditi N; Bardaro Jr, Michael F; Camilloni, Carlo et al. (2016) Structure of a low-population binding intermediate in protein-RNA recognition. Proc Natl Acad Sci U S A 113:7171-6
Hopping, Gene; Kellock, Jackson; Barnwal, Ravi Pratap et al. (2014) Designed ?-sheet peptides inhibit amyloid formation by targeting toxic oligomers. Elife 3:e01681
Hsu, Peter L; Yang, Fan; Smith-Kinnaman, Whitney et al. (2014) Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA polymerase II CTD. J Mol Biol 426:2970-81
Smith-Kinnaman, Whitney R; Berna, Michael J; Hunter, Gerald O et al. (2014) The interactome of the atypical phosphatase Rtr1 in Saccharomyces cerevisiae. Mol Biosyst 10:1730-41
Sperber, Henrik; Beem, Alan; Shannon, Sandra et al. (2014) miRNA sensitivity to Drosha levels correlates with pre-miRNA secondary structure. RNA 20:621-31
Chen, Yu; Varani, Gabriele (2013) Engineering RNA-binding proteins for biology. FEBS J 280:3734-54
Barnwal, Ravi Pratap; Lee, Susan D; Moore, Claire et al. (2012) Structural and biochemical analysis of the assembly and function of the yeast pre-mRNA 3' end processing complex CF I. Proc Natl Acad Sci U S A 109:21342-7
Walbott, Hélène; Machado-Pinilla, Rosario; Liger, Dominique et al. (2011) The H/ACA RNP assembly factor SHQ1 functions as an RNA mimic. Genes Dev 25:2398-408

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