CLEVELAND – A team of researchers from Case Western Reserve University have found a way to measure key features of RNA-binding proteins in cells – a finding that could advance our understanding of how gene activity disturbed in cancer, neurodegenerative disorders or diseases.
RNA – short for ribonucleic acid – carries genetic guidance within the body. RNA-binding proteins play an important role in the regulation of gene expression. Scientists already knew that the way these proteins work depends on their “binding kinetics,” a term that describes how often they give birth to a site in RNA, and how long they stay there.
To date, researchers have not been able to quantify the kinetics of RNA-binding proteins in cells. But Case Western Reserve researchers answered this long question in RNA biology. The findings open the door to biochemical understanding of RNA protein interactions in cells.
By understanding the kinetics, researchers can quantitatively predict how RNA-binding proteins regulate the expression of thousands of genes, which is crucial for developing strategies that focus on RNA protein interactions for medicinal purposes.
“The study marks a major step toward understanding how gene activity is regulated and how you devised ways to correct errors in this regulation in diseases such as cancer, neurodegenerative disorders or diseases, “said Eckhard Jankowsky, lead author of the study and professor of biochemistry at the university ‘s School of Medicine and director of the school’ s RNA Center for Science and Medicine.
Their study, “The kinetic landscape of RNA-binding proteins in cells,” was published Feb. 10 in Nature. Funding from the National Institute of General Medical Sciences and the National Science Foundation supported the research.
The co-authors, all from Case Western Reserve, are: Deepak Sharma research association; graduate students Leah Zagore, Matthew Brister and Xuan Ye; Carlos Crespo-Hernández, professor of chemistry; and Donny Licatalosi, associate professor of biochemistry and member of the Center for RNA Science and Medicine.
To measure the kinetics of RNA binding proteins, the researchers used a laser that emits ultra-short pulses (femtosecond) of ultraviolet light to cross-link the RNA-binding protein called DAZL to several thousand binding sites in RNAs. (DAZL, short for Deleted in Azoospermia-Like, is involved in germ cell development.) They then used a high-throughput series to measure the cross-linked RNA change over time and determined the binding kinetics of DAZL at thousands of link sites.
The resulting “kinetic landscape” allowed the researchers to decode the link between binding DAZL and its effect on RNAs.
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