Rui Zhao
University of Colorado Denver/Anschutz Medical Campus, CO·Biochemistry
Human genes are written in pieces: stretches that code for protein are interrupted by stretches that must be cut out before the instructions can be used. This editing step, called pre-mRNA splicing, is carried out by the spliceosome, a large machine built from RNA and protein.
- Fields
Biochemistry
Biophysics
Pharmacology
- Topics
pre-mRNA splicing
spliceosome
U1 snRNP
- Grants
- 2 known grants, through May 2027
What they work on
- Determine how the spliceosome recognizes alternative 5' splice sites, the choice points at the start of an intron, and how that recognition can be modulated, using structural, biochemical and genetic or genomic approaches.
- Work out the mechanism of exon definition, by which the splicing machinery treats a coding segment as a unit rather than reading each boundary independently.
- Establish how splicing is coupled to transcription, the copying of RNA from DNA, and what that coupling contributes to gene expression.
- Test the feasibility of resolving how splicing-modifying small molecules act, using cryo-electron microscopy to image the compound bound to its target complex of the U1 snRNP subunit and RNA.
- Develop biochemical assays of these modulators on the U1-RNA complex that can guide optimization of compounds designed to lower huntingtin protein in Huntington's disease.
More about the research
Splicing is essential in all organisms with a nucleus, and mistakes in it cause inherited disorders and contribute to many diseases. Work in this lab spans both sides of the problem: how the spliceosome chooses where to cut, and how small drug-like molecules can be used to redirect those choices in patients.
Why it matters
Faulty splicing underlies genetic disorders and many other diseases, so a clearer picture of how the spliceosome makes its decisions could open new therapeutic routes. More immediately, understanding how splicing-modifying small molecules engage the U1 subunit and RNA could help chemists refine compounds aimed at lowering huntingtin protein in Huntington's disease, where one candidate was already stopped for nerve toxicity, and could inform similar drugs for other neurological conditions.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Clara Kielkopf
University of Rochester, NY·Biochemistry
Compare how recurrent U2AF2 mutations found in neurodevelopmental disorders and in cancers affect RNA binding and splicing, using structural methods and pre-mRNA splicing assays in human cells.
Scott Bailey
Johns Hopkins University, MD·Biochemistry
Determine how CRISPR-associated proteins use small guide RNAs to locate and destroy foreign DNA or RNA in prokaryotes, using cryo-EM structures together with biochemical, biophysical and cell-based assays.
Jack Dunkle
University of Alabama, AL·Biochemistry
Test whether mismatches at specific sensitive positions in the guide RNA-target RNA duplex shut down interference by the Cas10-Csm complex, defining the accuracy rules for RNA-targeting Type III CRISPR-Cas systems.
The school
University of Colorado Denver/Anschutz Medical Campus: 41 labs on PI Pages, $766M a year on research, 205 research doctorates a year.
More about University of Colorado Denver/Anschutz Medical Campus
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