Moving Beyond a Classic Role of MicroRNAs

Image courtesy of: When microRNAs activate translation. Nature Methods 2008; 5(2): 122-3.

The 2009 Scaringe Award from the RNA Society was awarded to Shobha Vasudevan, post­doctoral fellow in Joan Steitz’s laboratory in the Molecular Biophysics and Biochemistry Depart­ment. Every year, one Scaringe Award is given to a postdoctoral fellow and one to a graduate student for outstanding achievements in RNA research. The award is one of the most prestigious inter­national prizes in RNA biochemistry.

“It is an honor to be considered among all the RNA society post-doctoral fellows,” remarked Vasudevan. In addition to the all-expense paid trip to the annual international meeting of the RNA Society at the University of Wisconsin, Vasude­van was also awarded the opportunity to write a review of her research for publication in the distinguished journal RNA. Vasudevan’s review will likely focus on her research on microRNAs, particularly her discovery of their novel roles in quiescent frog cells.

MicroRNAs are single-stranded RNA segments (21-23 nucleotides in length) that have been shown to downregulate messenger RNA (mRNA) trans­lation. However, Vasudevan demonstrated that within certain circumstances, microRNAs can upregulate translation.

“I was working on particular sequence elements in mRNA called AU-rich elements, which regulate translation, when I accidently discovered a condi­tion by which translation is activated. I was sur­prised to find that components of the microRNA pathway are direct regulators of translation activa­tion under these conditions.”

Upon discovering a new role for microRNA, Vasudevan began studying the exact circumstances in which upregulation occurs. “MicroRNAs have the potential to switch from their traditional role as repressors to function as activators under the right conditions,” explained Dr. Vasudevan. “They respond to changes in the cell cycle and cause activation when the cells are quiescent.”

Quiescent cells are those that are not dividing nor differentiating but have the capacity to return to the proliferative cycle. Cell quiescence provides the key conditions necessary for the observed microRNA activation. According to Vasudevan, quiescent cells have a very distinct gene expres­sion profile that involves the exclusive synthesis of factors that are potential targets for microRNA activation. It is the activation of these certain targets that enables a cell to maintain quiescence.

Many natural cells in the body, unlike tumor cell cultures grown in the laboratory, are quies­cent. Therefore, Vasudevan’s novel findings are significant to understanding gene regulation in vivo. Furthermore, since microRNAs are impor­tant regulators in many diseases from cancer to autoimmune diseases to developmental disorders, these findings also shed a new light on microRNA research.

Currently, Vasudevan is continuing microRNA research in the Steitz laboratory using frog oocy­tyes. These female germ line cells are an amenable in vivo system for microRNA studies because they both remain quiescent for long periods of time, but also undergo profound developmental changes.

However, she will soon be departing Yale to becoming a principal investigator at the Mas­sachusetts General Hospital Cancer Center. “It’s quite interesting learning the many aspects of starting a new lab; there is a lot of excitement and also a lot of responsibility. Hopefully, it will be a great opportunity to go forward and progress in my research.”

As Vasudevan’s experience shows, it is critical to review data and to think beyond accepted models. Only with careful eyes can major advances in understanding the novel roles of biological factors and sequences be made.