Mathematical Biology Seminar
Jeff Morgan, UU Biochemistry
Wednesday,Oct. 5 2022
3:05pm in LCB 225
How cells sense: probing the RNA-metabolite interactome and its role in gene regulation
Abstract:
The ability for cells to sense changes in their metabolic environment is built from the series of
one-to-one interactions that occur between specific biomolecules and, further, what information is
conveyed by the formation and dissolution of these interactions across space and time. Despite the
regulation and dysregulation of these interfaces being the cause of and treatment for numerous
diseases, we are lacking in a holistic understanding of the basic underlying question: what
interacts with what in our cells? For example, RNAs and metabolites can interact with high affinity
and specificity; yet, our knowledge of RNA-metabolite interactions in eukaryotes?and what their
functions might be?is, effectively, nonexistent.
To interrogate the human RNA-metabolite interactome, I performed structure probing and
high-throughput sequencing to determine which RNAs in a complex mixture (e.g. poly(A)+ RNA from
HEK293 cells) exhibit robust changes in structure when incubated with a 410-compound human
metabolite library. An analysis of 4300 5-prime ends of human mRNAs revealed ?70 that exhibit
significant, metabolite-dependent conformational changes. Utilizing a high-throughput equilibrium
dialysis platform, I identified the specific metabolites bound by eight of these RNAs. Some
interactions show logical connections between bound metabolite and gene function and have
functional consequences on gene expression in vitro and in cells, which suggests RNAs may indeed be
used to sense metabolic changes in eukaryotic systems.
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