Micro RNA and the importance of basic biology
By Mark Wanner
It wasn’t that long ago that RNAs were regarded as rather static molecules. The information encoded in DNA is transcribed to messenger RNA (mRNA), which squeezes out of the nucleus to ribosomes in the cell, where proteins are made. Transfer RNAs (tRNA) in turn truck amino acids to the ribosomes in the correct order for protein production. These are crucial functions to be sure, but also straightforward. RNA was, to put it bluntly, kind of boring from a research standpoint.
How things have changed. As it turns out, there are many kinds of RNAs performing other vital, often complex functions in cells. And much of our understanding of one of the most intriguing forms — micro RNA (miRNA) — is thanks to the work of V. Narry Kim, Ph.D., who has made many significant contributions to the field since receiving her Ph.D. fewer than 20 years ago. Dr. Kim now directs the Center for RNA Research at the Institute for Basic Science, Seoul National University, and was presented with the Chen Award at the recent Human Genomics Meeting in Barcelona for her outstanding work.
Over breakfast before the last day of the meeting, Kim discussed her interest in miRNA and the value of understanding biological details.
miRNAs are short [note: usually 21-25 nucleotides in length] RNAs that don’t code for proteins but are nonetheless highly conserved across species. They regulate many targets, such as in mRNA suppression, where they prevent an mRNA from being translated into a protein. miRNAs are in turn regulated by many other parts of the system. We know that they’re very important because they’re conserved, and also experimentally. For example, when we knock them out in mice, the mice get very weird, to be non-technical.
Earlier we developed a model for how miRNAs are made in the cell and how that process is regulated. We’ve now expanded our program into multiple projects. In one, we’re looking at aspects of miRNA function in cells, such as how they help determine how stem cells differentiate into different mature cells and tissues. We’re also researching the structure of miRNAs, both alone and in complex with proteins, and determining how miRNAs are recognized and processed within cells. This project will help with miRNA gene annotation as well, as we can use knowledge of how they’re processed to improve database entries, many of which are currently inaccurate or incomplete. Finally, we’re studying different kinds of RNA modification and post-transcriptional control. RNA-protein interaction is important, and there are many different kinds of interactions, with many functions. We’re developing methods to map out the sites on the molecules that interact and determine the RNA sequences that are recognized by proteins.
We work in mammalian cells (human and mouse) mostly, but because miRNAs are so highly conserved, we use other animal models such as Drosophila and zebra fish to make comparisons and focus on what’s conserved between them.
It’s true that we’re looking at fundamental biology at this time. But the mechanisms can be applied to any biological context: development, disease, cancer, degeneration. RNAs play many roles in many different processes in the cell, and you need to elucidate the basic rules that apply — you need to understand how it actually works — before you can know what happens when it goes wrong. That said, some of my students are interested in developing focused applications for RNA-based research after their work in my lab. So we’re building a foundation, but the knowledge we gain may be very useful for more translational or applied research in the years ahead.