RNA Innovation Seminar: Joseph Yesselman, Ph.D. — University of Nebraska

The University of Michigan Center for RNA Biomedicine Seminar Series will host Joseph Yesselman, Ph.D., as part of the 2024 – 2025 RNA Innovation Seminar Series.

Joseph Yesselman, Ph.D.
Assistant Professor, Chemistry
University of Nebraska

Date and Time: Monday, October 7 | 4 p.m.
In-person: Kahn Auditorium, BSRB
Hybrid Option: Click here to join the Zoom.

Talk Title: “High-throughput determination of RNA tertiary contact thermodynamics by quantitative DMS chemical mapping”

Abstract:
Structured RNAs often contain long-range tertiary contacts that are critical to their function. Despite the importance of tertiary contacts, methods to measure their thermodynamics are low throughput or require specialized instruments. Here, we introduce a new quantitative chemical mapping method (qMaPseq) to measure Mg2+-induced formation of tertiary contact thermodynamics in a high-throughput manner using standard biochemistry equipment. With qMaPseq, we measured the ΔG of 98 unique tetraloop/tetraloop receptor (TL/TLR) variants in a one-pot reaction. These results agree well with measurements from specialized instruments (R2=0.64). Furthermore, the DMS reactivity of the TL directly correlates to the stability of the contact (R2=0.68), the first direct evidence that a single DMS reactivity measurement reports on thermodynamics. Combined with structure prediction, DMS reactivity allowed the development of experimentally accurate 3D models of TLR mutants.  These results demonstrate that qMaPseq is broadly accessible, high-throughput, and directly links DMS reactivity to thermodynamics.

Please visit the Yesselman Lab website to learn more about Dr. Yesselman and his work.