Clara Kielkopf
University of Rochester, NY·Biochemistry
Before a gene's message can be read, the cell must cut out the non-coding stretches of its RNA copy and stitch the coding parts together. This process is called pre-mRNA splicing.
- Fields
Biochemistry
Biophysics
Genetics
- Topics
pre-mRNA splicing
3' splice site
spliceosome
- Grants
- 1 known grant, through Apr 2027
What they work on
- 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.
- Determine how the timing of SF3B1 phosphorylation and dephosphorylation is coordinated with U2AF2 leaving the complex before splicing, using co-immunoprecipitation, calorimetry and fluorescence assays.
- Reveal how U2AF2, U2AF1 and SF1 are arranged on the 3′ splice site to ensure accurate splicing, using X-ray crystallography and cryo-electron microscopy.
- Measure transcriptome-wide effects of disease mutations in these splicing factors using RNA sequencing in human cells.
More about the research
The cell must find the exact cut sites, and errors in this step are common in cancers and other diseases. This project asks how the splicing machinery recognizes the 3′ splice site, the cut site at the end of each non-coding stretch, at the structural level of atoms and molecules.
Why it matters
Splicing errors drive many cancers and some neurodevelopmental disorders. Knowing exactly how splicing proteins recognize their targets, and how disease mutations disrupt them, could provide the molecular context needed to develop personalized medicines for patients whose disease involves faulty splicing.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Rui Zhao
University of Colorado Denver/Anschutz Medical Campus, CO·Biochemistry
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.
Kotaro Nakanishi
Ohio State University, OH·Biochemistry
Determine how AGO2 and AGO3 loaded with cleavage-inducing tiny RNAs (cityRNAs) recognize the sequence just upstream of their target site and cut target RNA, using structural studies and RNA sequencing.
Stephanie Gates
University of Missouri-Columbia, MO·Biochemistry
Dissect how the Hsp70/CHIP/BAG-1 chaperone complex affects each step of proteasomal degradation, including ubiquitin tagging, substrate binding and breakdown, using in vitro assays with purified proteins.
The school
University of Rochester: 38 labs on PI Pages, $492M a year on research, 308 research doctorates a year.
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