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Clara L. Kielkopf, Ph.D.
Clara L. Kielkopf, Ph.D.

Clara L. Kielkopf, Ph.D.

Clara L. Kielkopf, Ph.D.


Locations

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, NY 14642
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phone

Office

(585) 273-4799

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Fax

(585) 275-6007

Research

The Kielkopf lab investigates the molecular structures and interactions among key pre-mRNA splicing factors in human genetic diseases and hematologic malignancies (Trends Genetics 2017). Our recent structures of U2AF2 bound to a range of splice site signals provide a basis for understanding disease-causing mutations in the splice sites of gene transcripts (PNAS 2014; Nature Commun. 2016). As a step towards viewing the architecture of multi-subunit pre-mRNA splicing factor complexes, we revealed phosphorylation-induced conformational changes in the splicing factor subunit SF1 bound to U2AF2, and demonstrated that the phosphorylated interface is essential in vivo (Structure 2013). We have further shown that recurrent, cancer-associated mutations of U2AF1 alter its RNA interactions (Leukemia 2014; PLOS Genetics 2017). Now, our immediate goal is to determine roadmaps of the key interactions among higher order 3' splice site complexes, and in future phases of the project, assist the development of therapeutics targeted at the level of pre-mRNA splicing.

We are grateful to the following organizations for research funding:

National Institutes of Health:
R01 GM070503: Molecular Recognition During pre-mRNA Splicing
R01 GM117005: Structural Control of Human Co-factors for Retroviral Gene Expression

Edward P. Evans Foundation:
Research Discovery Grant: Structural mechanisms & targeting of MDS-relevant pre-mRNA splicing factors

Publications:

Jenkins JL, Kielkopf CL. "Splicing Factor Mutations in Myelodysplasias: Insights from Spliceosome Structures." Trends in genetics : TIG.. 2017 May 0; 33(5):336-348. Epub 2017 Mar 31.

Chatrikhi R, Wang W, Gupta A, Loerch S, Maucuer A, Kielkopf CL. "SF1 Phosphorylation Enhances Specific Binding to U2AF(65) and Reduces Binding to 3'-Splice-Site RNA." Biophysical journal.. 2016 Dec 20; 111(12):2570-2586.

Loerch S, Kielkopf CL. "Unmasking the U2AF homology motif family: a bona fide protein-protein interaction motif in disguise." RNA.. 2016 Dec 0; 22(12):1795-1807.

View All Publications

Links:

Lab Website

Center for RNA Biology