This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The way in which genes are expressed in all of our cells is a highly regulated, complex process involving hundreds of protein factors and several non-coding snRNAs. The process of pre-mRNA splicing is required to remove stretches of RNA called introns, which if not removed would interfere with proper expression of that gene. Almost all human genes contain introns and their faithful and rapid removal is required for proper functioning. The machinery in eukaryotic cells charged with the removal of introns is called the spliceosome, a collection of RNAs and many proteins that rearranges several times during the course of a single intron removal, recruiting factors and ejecting others in a highly coordinated manner. The recent discovery of the penta-snRNP in yeast cells has challenged a paradigm in the mechanism of spliceosome assembly, specifically, that the machinery is largely pre-assembled and that the rearrangements occur within this pre-assembled complex. The single-celled eukaryotic organism Saccharomyces cerevisiae will be used to study the process of spliceosome assembly and the pre-mRNA splicing reaction as it is amenable to genetic and biochemical analysis and executes the pre-mRNA splicing reaction in a way that is chemically identical to the human splicing reaction. This CAREER project will address the mechanism of spliceosome assembly and the means by which the penta-snRNP engages its pre-mRNA substrate. Compositional and functional analyses of the early splicing intermediates will allow a comprehensive biochemical and genetic analysis of the initial events in spliceosome assembly. In conjunction with the Austin Independent School District, this project also endeavors to initiate and execute a comprehensive outreach program involving area high school teachers, administrators and students to provide exposure of interested junior and senior students to modern molecular biology and the educational and research options available to them.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR011823-13
Application #
7723701
Study Section
Special Emphasis Panel (ZRG1-CB-H (40))
Project Start
2008-09-01
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
13
Fiscal Year
2008
Total Cost
$8,075
Indirect Cost
Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Xavier, Marina Amaral; Tirloni, Lucas; Pinto, Antônio F M et al. (2018) A proteomic insight into vitellogenesis during tick ovary maturation. Sci Rep 8:4698
Hollmann, Taylor; Kim, Tae Kwon; Tirloni, Lucas et al. (2018) Identification and characterization of proteins in the Amblyomma americanum tick cement cone. Int J Parasitol 48:211-224
Stieg, David C; Willis, Stephen D; Ganesan, Vidyaramanan et al. (2018) A complex molecular switch directs stress-induced cyclin C nuclear release through SCFGrr1-mediated degradation of Med13. Mol Biol Cell 29:363-375
Seixas, Adriana; Alzugaray, María Fernanda; Tirloni, Lucas et al. (2018) Expression profile of Rhipicephalus microplus vitellogenin receptor during oogenesis. Ticks Tick Borne Dis 9:72-81
Wang, Zheng; Wu, Catherine; Aslanian, Aaron et al. (2018) Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway. Elife 7:
Luhtala, Natalie; Aslanian, Aaron; Yates 3rd, John R et al. (2017) Secreted Glioblastoma Nanovesicles Contain Intracellular Signaling Proteins and Active Ras Incorporated in a Farnesylation-dependent Manner. J Biol Chem 292:611-628
Thakar, Sonal; Wang, Liqing; Yu, Ting et al. (2017) Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation. Proc Natl Acad Sci U S A 114:E610-E618
Jin, Meiyan; Fuller, Gregory G; Han, Ting et al. (2017) Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress. Cell Rep 20:895-908
Ogami, Koichi; Richard, Patricia; Chen, Yaqiong et al. (2017) An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression. Genes Dev 31:1257-1271
Ju Lee, Hyun; Bartsch, Deniz; Xiao, Cally et al. (2017) A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nat Commun 8:1456

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