Paulina gives a brief insights into miRNAs, the discovery of which was appreciated by the recent Nobel Prize in physiology or medicine, and explains why she studies miRNAs in the liver.
The exciting 2024 Nobel Calling last week began with an award to Victor Ambros and Gary Ruvkun for their discovery of microRNA and its role in post-transcriptional gene regulation. This groundbreaking discovery unveiled a new layer of complexity in how genes are controlled within our cells.
In the genetic information stored in the DNA of our cells (and in every living organism), there are instructions for the proteins that should be produced. The proteins arise through a process called gene expression, where first the DNA is transcribed into messenger RNA (mRNA), and then mRNAs are translated so that proteins are synthesized.
Despite having the same DNA, different cells in our body perform unique functions because they express different sets of genes (Figure 1). MicroRNAs are tiny RNA molecules that control protein production in organisms by switching off the expression of specific genes, ensuring that each cell type synthesizes a specific set of proteins (1,2).
Figure 1. The flow of genetic information from DNA to mRNA to proteins. The identical genetic information is stored in DNA of all cells in our bodies. This requires precise regulation of gene activity so that only the correct set of genes is active in each specific cell type. © The Nobel Committee for Physiology or Medicine. Ill. Mattias Karlén https://www.nobelprize.org/prizes/medicine/2024/press-release/
miRNAs against cancer
The discovery of microRNA has revolutionized our understanding of gene regulation and opened up new possibilities for therapeutic interventions. One of the most exciting applications of microRNA therapeutics is in the fight against cancer. Cancer cells often exhibit uncontrolled gene expression, leading to unchecked growth and proliferation. By engineering synthetic microRNAs, it is possible to specifically modulate gene expression and silence only cancer-promoting genes3.
For us, microRNAs have special significance because we are studying their role in liver development and disease. MicroRNAs, such as miR-34a, regulate many liver genes, and we are investigating the exact role of miR-34a in gene regulation at different developmental stages to learn more about how liver cells know their fate and mature. It is also important to study the function of miR-34a in liver and other cancers to develop innovative treatments that could stop cancer in its tracks (Figure 2).
Figure 2. Colon cancer cells with introduced miR-34a (in red). Nuclei are in blue, cytoplasm is in white.
Read more about microRNAs:
1. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843-854. doi:10.1016/0092-8674(93)90529-y
2. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75(5):855-862. doi:10.1016/0092-8674(93)90530-4
3. Rupaimoole, R., Slack, F. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16, 203–222 (2017). https://doi.org/10.1038/nrd.2016.246
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