In eukaryotes, the Central Dogma of molecular biology is comprised of three steps: transcription, splicing, and translation. The genetic information stored in DNA is transcribed into precursor messenger RNA (pre-mRNA). Splicing pre-mRNA, involving non-coding intron remova,l and exon ligation through two sequential transesterification reactions, are the central steps of eukaryotic gene expression. In human cells, more than 95% of genes contain introns, which need to be correctly spliced. Due to splicing, a single gene can encode more than one protein, significantly expanding the complexity of life.
Ruixue Wan chose to study biology during university because of her long-lasting interest in this field, ever since she was a kid. Upon graduation, she was admitted to Dr. Yigong Shi’s team for her master’s degree at Tsinghua University.
“As soon as I started working in the lab, the first research topic I came across was RNA splicing. In the process of working on this subject, there has been an on-going revolution in structural biology - the adoption of cryo-electron microscopy,” Ruixue said.
At the end of 2014, Ruixue expanded her vision by further investigating and exploring the structure of the entire spliceosome complex from a small component in the spliceosome. By 2014, the resolution of a complete spliceosome structure was about 29～40 angstroms. Only ambiguous shapes of spliceosome can be observed, such as triangles and rectangles. According to her, many clues are fetched with cell biology or biochemistry means, but it is still very difficult to directly see the structure of the spliceosome or reveal the splicing process systematically and wholesomely.
Looking forward, Ruixue is excited that there are still lots of questions waiting to be uncovered in the future. One of her future research goals is to directly see how the spliceosome in the cell is regulated and how it performs its functions. She expects the further adoption of cryo-electron microscopy which can help the field better understand and see protein structure.
“There are lots of research directions and opportunities, such as RNA splicing, using spliceosome for medicine design, and some other disease-related fields,” Ruixue said. “What we have been doing is just a small step in a long journey.”