Dr. Konarska was born in Poland and received her M.Sc. in genetics from the University of Warsaw in 1979. In 1983, she received her Ph.D. in biochemistry from the Institute of Biochemistry and Biophysics at the Polish Academy of Sciences in Warsaw. She joined the Center for Cancer Research at the Massachusetts Institute of Technology (MIT) as a postdoc in 1984 and became a research associate at MIT in 1987. Dr. Konarska came to The Rockefeller University as assistant professor in 1989 and became associate professor in 1994 and professor in 2000. Since 2013 she is also affiliated with the Center for New Technologies of the University of Warsaw.
In 1992, Dr. Konarska received the Monique Weill-Caulier Career Scientist Award. She received the Lucille P. Markey Scholar Award in 1987 and the Jakub Karol Parnas Award of the Polish Biochemical Society in 1985.
RECOMB 2015 keynote talk: Analysis of spliceosome function: from the mechanisms of catalysis to interconnections within global networks of gene expression
Pre-mRNA splicing, a process during which introns are removed from eukaryotic pre-mRNAs, can generate multiple forms of mRNA products. Three sites in pre-mRNA substrates, the 5' and 3' splice sites and the branch site, participate directly in two consecutive transesterification reactions of splicing, catalyzed by a single enzyme, the spliceosome. Recognition of these sites and their proper positioning within the spliceosome determine the specificity and efficiency of the reaction; alterations in splice site selection lead to alternative splicing. Using genetic analysis in yeast, Saccharomyces cerevisiae, we analyze the mechanism of this process. The spliceosome conformations supportive of the first and the second step catalysis exist in competition; numerous mutant alleles in spliceosomal components can improve one of the splicing steps by stabilizing the corresponding spliceosomal conformation, but inhibit the other step. If the active sites for the two splicing reactions are related, then substrates should be positioned similarly for the two steps. Indeed, I will present evidence for the branch site and the 3' splice site binding to the same site at the catalytic center during the first and second step, respectively. This model of interactions at the spliceosomal catalytic center has important implications for substrate selection for splicing.
Genetic analysis can also help to study other nuclear reactions that affect splicing. I will describe an example of a genetic screen to identify mutants that improve splicing of introns with defective 5' splice site. Among the isolated alleles are not only mutant forms of spliceosome components, but also mutants of factors implicated in a wide range of mRNA biogenesis reactions – from transcription, through processing, to mRNA transport – pointing to a delicate network of interactions between different nuclear processes.