By Irene Hsiao
Chemical modifications to RNA are increasingly understood to regulate the translation of RNA into proteins and thus protein activity in living organisms. To aid our understanding of how these modifications affect biological processes, the labs of Chuan He and Bryan Dickinson have developed a precise and robust technique for detecting the presence and location of these modifications at a single-base resolution. In “Evolution of a reverse transcriptase to map N1-methyladenosine in human messenger RNA,” published 23 September 2019 in Nature Methods, they present a system for evolving reverse transcriptases that install a mutation in place of the nucleotide where the modification is found. Using their method, they have discovered hundreds of sites on human mRNA for one such modification, m1A, and can estimate the proportion of m1A at any given site in mammalian cells.
A joint postdoctoral fellow in the He and Dickinson labs, first author Huiqing (Jane) Zhou became interested in genetics as a high school student in Tai’an, China. Her father, a chemist, encouraged her to begin her studies on a molecular level. “It was a good suggestion,” says Zhou. She received her BS in chemistry on a China National Scholarship at Nankai University before pursuing graduate work studying the structure and dynamics of oligonucleotides using NMR spectroscopy at the University of Michigan at Ann Arbor and Duke University. Her thesis, “Occurrence and function of Hoogsteen base pairs in nucleic acids” was completed under the supervision of Professor Hashim Al-Hashimi.
A Chicago Fellow at the University of Chicago since 2017, Zhou has enthusiastically directed her research towards biological questions. “People were very supportive in both labs to get me going,” she says. “I had never touched or purified proteins before—I had never touched any cells before!” She acknowledges the importance of the collaborative environment at Chicago, crediting Simone Rauch, a graduate student in the Dickinson lab, with introducing her to the techniques she needed early in the process, and members of the He lab for training in sequencing and bioinformatics. “There were many steps to optimize,” she says. “The rewarding part has been to work through every single step and understand why and how it works.”
“My interest is eventually to make more discoveries in biology,” says Zhou. “Currently we have been working with lab cell lines. We are hoping to apply this method to more interesting biological contexts, such as tissues and brain samples, to answer specific questions about biological processes.”