“Decoding Terminators: Synthetic terminator designs enabled by a comprehensive analysis of plant terminators”

Abstract: The 3’ end of a gene, often called a terminator, modulates mRNA stability, localization, translation, and polyadenylation. Here, we adapted Plant STARR-seq, a massively parallel reporter assay, to measure the activity of over 50,000 terminators from the plants Arabidopsis thaliana and Zea mays. We characterize thousands of plant terminators, including many that outperform bacterial terminators commonly used in plants. Terminator activity is species-specific, differing in tobacco leaf and maize protoplast assays. While recapitulating known biology, our results reveal the relative contributions of polyadenylation motifs to terminator strength. We built a robust computational model to predict terminator strength and used it to conduct in silico evolution that generated optimized synthetic terminators. Additionally, we discover alternative polyadenylation sites across tens of thousands of terminators; however, the strongest terminators tend to have a dominant cleavage site. Our results establish features of plant terminator function and identify strong naturally occurring and synthetic terminators.

Bio: Sayeh Gorjifard joined the Genome Sciences Department at the University of Washington as a graduate student in 2018. She graduated in the fall of 2023 and has since continued as a one-year postdoctoral scholar to conclude ongoing research. Sayeh received her undergraduate degrees in Chemistry and Art from Dartmouth College in New Hampshire, where she focused on manganese-catalyzed reactions to 2-cyanoindoles. Following her undergraduate studies, she researched as a CRTA fellow at the National Cancer Institute, studying the effect of the gut microbiome on the response to cancer therapy. Subsequently, she earned her Master’s degree in Biotechnology from Johns Hopkins University as a Molecular Target and Drug Discovery Fellow. During her master’s program, she played a role in developing a pharmacogenomic pipeline to predict the most effective drug combinations for Multiple Myeloma patients. Sayeh’s journey continued at the UW Genome Sciences for her Ph.D., where she studied CRISPR technology development and plant regulatory grammar.

The UW Data Science Seminar is an annual lecture series at the University of Washington that hosts scholars working across applied areas of data science, such as the sciences, engineering, humanities and arts along with methodological areas in data science, such as computer science, applied math and statistics. Our presenters come from all domain fields and include occasional external speakers from regional partners, governmental agencies and industry.

The 2023-2024 seminars will be held in person, and are free and open to the public.