miR-31, an evolutionarily conserved microRNA, has been studied in different contexts, such as myogenesis, skeletogenesis and cancer; however, its role in post-transcriptional regulation during development is still unclear. In a new study, Jia Song and colleagues find that miR-31 regulates local translation of cytoskeletal remodelling transcripts at the mitotic spindle to ensure proper cell division during sea urchin embryogenesis. To find out more about the story behind the paper, we caught up with first author Carolyn Remsburg and Jia Song, Professor at the University of Delaware, USA.

Jia Song (left) and Carolyn Remsburg (right) with purple sea urchins

Jia, can you give us your scientific biography and the questions your lab is trying to answer?

JS: As a graduate student, I was interested in translational medical research. I was examining antifungal drug resistance in Candida albicans. As I progressed through my graduate studies, I became more and more appreciative of the importance of basic science research. As a postdoctoral researcher, I switched to the field of developmental biology, an area that has continued to intrigue and amaze me. My own laboratory at the University of Delaware focuses on understanding post-transcriptional regulation mediated by microRNAs during early development, using the sea urchin embryo as a model.

Carolyn, how did you come to work in the lab and what drives your research today?

CR: I started my career as a veterinarian and was in practice for 10 years. During that time, I realized that I wanted to pursue basic science research. So, I decided to go back to school to get my PhD. After starting at the University of Delaware, I chose to work in Dr Song's lab, because I think trying to understand how a single cell is able to develop into a fully functional organism is fascinating. As my research progressed, the idea that RNA can have so many levels of post-transcriptional regulation, such as where it is localized, when it should be translated and when it should be degraded, really reminded me that biological processes are always more complex than we thought at first glance.

What is the background of the field that inspired your work?

JS: When I started my own laboratory in 2010, my first doctoral student made the interesting, fortuitous observation that miR-31 seems to be associated with the mitotic spindle in early cleavage stage embryos. Later in development, miR-31 is ubiquitous. At the time, we did not know how to explain the localization of miR-31 and this work laid dormant in my lab for over 10 years. Upon high-throughput analysis of testing the function of miR-31, we noticed that many of its targets are involved in cytoskeletal remodelling. We tied this result to our observation of the cell cycle-dependent localization of miR-31 to reveal that miR-31 mediates local translation at the mitotic spindle.

Can you give us the key results of the paper in a paragraph?

JS: miR-31 is an evolutionarily conserved microRNA. We discovered miR-31 and some of its validated target transcripts are enriched on the mitotic spindle of the dividing sea urchin embryo and mammalian cells. miR-31 inhibition led to developmental delay correlated with increased cytoskeletal and chromosomal defects. We identified miR-31 to directly suppress several actin remodelling transcripts, including β-actin, Gelsolin, Rab35 and Fascin. We found miR-31 inhibition leads to significant increase of newly translated Fascin at the spindle of dividing sea urchin embryos. Forcing Fascin translation to occur at the cell periphery resulted in significant developmental and chromosomal segregation defects, revealing the importance of the regulation of local translation by miR-31 at the mitotic spindle. We also observed miR-31 and new translation of Fascin in the mitotic spindle of dividing mammalian cells, suggesting that miR-31-mediated post-transcriptional regulation at the mitotic spindle may be an evolutionarily conserved regulatory mechanism of mitosis.

A cleavage stage sea urchin embryo has miR-31 and its target transcript co-localized to the cell periphery and the mitotic midzone. Green, miR-31; red, Fascin; magenta, microtubules; cyan, DNA.

A cleavage stage sea urchin embryo has miR-31 and its target transcript co-localized to the cell periphery and the mitotic midzone. Green, miR-31; red, Fascin; magenta, microtubules; cyan, DNA.

Carolyn, when doing the research, did you have any particular result or eureka moment that has stuck with you?

CR: When we first started observing the in situ hybridization images showing that miR-31 and its target transcripts localized to the mitotic spindle, we did not know what to make of it. When we immunolabeled Fascin protein in miR-31-inhibited embryos and observed that it was enriched in the mitotic spindle, we realized that miR-31 may be inhibiting local translation at the mitotic spindle. That was probably one of the first experiments that led us to realize that something really interesting was happening!

That was probably one of the first experiments that led us to realize that something really interesting was happening!

Carolyn, what is next for you after this paper?

CR: I recently started my post-doc in a lab that studies meiosis using C. elegans as a model. I want to start my own lab in a PUI (primarily undergraduate institution), because I love interacting with students at a time when they are starting to think about their career choices. I want to offer them opportunities to experience research and how exciting it is.

Jia, where will this story take your lab next?

JS: This work revealed some answers but also posed more questions. For example, we are interested in knowing the functions of miR-31 targets that are needed to ensure proper mitosis. We are also interested in knowing how these RNAs are transported to the mitotic spindle.

Finally, let's move outside the lab – what do you like to do in your spare time?

JS: I enjoy hiking and traveling.

CR: I love traveling, knitting and spending time with my family.

Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.

E-mail: [email protected]

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miR-31-mediated local translation at the mitotic spindle is important for early development
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Development
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dev202619
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