First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Weiya Xu is first author on ‘ Transcription factor-like 5 is a potential DNA- and RNA-binding protein essential for maintaining male fertility in mice’, published in JCS. Weiya conducted the research described in this article while a PhD student in Xin Wu's lab at State Key Laboratory of Reproductive Medicine, Nanjing Medical University, P.R. China. Her current study is an investigation into the regulatory mechanisms during germline cell development, in particular, spermiogenesis.
How would you explain the main findings of your paper in lay terms?
In mammalian testes, male germ cells undergo a series of deformations, so the round sperm becomes a tadpole-like mature sperm, in a process called spermiogenesis. In this complex process, various factors and players are involved at both the transcriptional and post-transcriptional levels to ensure accurate assembly of sperm. In my work, we show that TCFL5 protein is one of these proteins. Loss of even half of Tcfl5 gene dose from the mouse chromosome leads to completely infertile male mice because of various malformations of the nucleus and acrosome, and/or axons of caudal flagellum in sperm. To explore the underlying mechanism, I conducted several large-scale screens to look for the downstream targets and the binding partners of TCFL5. Surprisingly, I found this protein actually serves as a protein that binds both RNA and DNA when I developed a unique method – the enhanced RNA–protein crosslinking immunoprecipitation (eCLIP) method. Therefore, my data show that TCFL5 functionally regulates sperm development at both transcriptional and post-transcriptional levels.
Were there any specific challenges associated with this project? If so, how did you overcome them?
I learned from the literature that the enhanced CLIP (eCLIP) assay is a very powerful technique to address whether TCFL5 has RNA-binding properties since it is neither restricted to radioactive labeling, nor uses cell lines, but still has a single-nucleotide resolution that allows protein–RNA binding to be interrogated. However, our laboratory was not set up for the protocols needed for this experiment at that time. I followed the protocols given in the literature and successfully completed the experiments with the help of other members in our lab. I sincerely thank them for their help.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
When I got the mass spectrometry results, I was surprised to find that most of the proteins interacting with TCFL5 are actually related to RNA processing, in spite of this protein initially being considered a transcription factor by us. This novel observation drove my interest in exploring its post-transcriptional regulation. Eventually, I proved that TCFL5 is a DNA- and RNA-binding protein.
Why did you choose Journal of Cell Science for your paper?
JCS has published many interesting papers in the field of spermatogenesis. Our laboratory has also published an article there before, and we chose the journal again because of its reputation in the field, professional editorial team and efficient turnaround time.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
My current supervisor, Dr Xin Wu encouraged me to become a person pursuing goals with early planning. He can grasp the key points of the problem, so when I deviated from the direct path, with his supervision, I was able to refocus on the things that I should pay attention to at the time.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
A sense of curiosity for unanswered questions and a tenacious personality helped me with my motivation for exploring real science. When I was first taking this subject, I knew nothing about spermiogenesis and other testis biology. I have now found that the TCFL5-knockout mice are infertile, and I am very interested and keen to know why. This ‘simple’ question drives me to learn more about reproductive biology and molecular biology and explore the underlying mechanism.
Who are your role models in science? Why?
I do not have a specific person as my role model. I appreciate those who are not easily defeated by difficulties and can reduce complex problems to simplicity.
What's next for you?
I leaving myself time to decide. At present, I am going to finish my PhD study first. Sometimes decisions can made in an instant.
Tell us something interesting about yourself that wouldn't be on your CV
Recently, I took a few tennis lessons and practiced forehands and backhands. I am very interested in the characteristics of this sport that requires full body participation. I didn't expect my backhand to be so good!
Weiya Xu's contact details: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China 210029.