When looking at small aspects of living things, especially cells, it can often be difficult to fully grasp the magnitude of regulation employed within them. We first learn the central dogma in high school biology. This is the core concept that DNA makes RNA and RNA makes protein. Despite this early education, it can be lost on many the biological methods that are employed to regulate this process. This regulation is very important when one considers the disastrous things that can occur when this process goes askew, such as cancer, or dysregulated cell death. Therefor it is very important to understand how these regulatory mechanisms work and employ tools to better understand them.
One of the most fascinating of these processes is the use of small RNAs, such as small interfering RNA (siRNA) or microRNA (miRNA) to interfere with the production of protein from messenger RNA (mRNA). One interesting note about miRNA is that they are highly conserved between kingdoms. This suggests that this mode of regulation has persisted through many eras of evolution (Ha et al., 2008). Most people start to get overwhelmed when they start to hear how many types of RNA there are, so I’ll try and outline the most important pieces to understand why work using these two types of RNA is very important within biological research.
Both siRNA and miRNA perform a process called RNA interference (RNAi), which inhibits the process of translating mRNA into the amino acids that make up a protein (Friedrich & Aigner, 2022). This occurs through complementary sequence binding and blocking the cellular processes that would ‘read’ the open mRNA sequence. These two small RNA work through slightly different methods, however, to keep it simple one can think of siRNA as having a more ‘specific’ mRNA target that they bind to, while miRNA have a more expansive group of targets, meaning they are likely to bind to several different mRNA targets.
Although both siRNA and miRNA have been shown to occur endogenously, it is typical for scientists to transfect these small RNA into a cell to inhibit regulatory genes and pathways involved in important health conditions. This transfection provides an opportunity to observe the effects small RNAs have on cellular processes with a greater degree of control. The FuGENE® SI Transfection Reagent is available at Promega for optimized transfection of small RNA into cells. For more information on how transfection of small RNA is important for a variety of cellular processes, please see our related technical article.
Work with small RNA molecules has helped scientists uncover regulatory mechanisms employed in a variety of important biological processes. These include vital understanding in the regulatory pathways involved in cancer progression, acquired resistance of immune responses, and most recently the production of five FDA approved therapeutics as of 2022 (Ahn et al., 2023; Bong et al., 2022; Wang et al., 2023). Due to the relatively straightforward mechanism these small RNAs employ for genetic regulation, they provide a fantastic mode of studying genetic regulation within the context of understanding how cells function. Small RNAs are a very exciting way forward to both understand cellular function and as a powerful therapeutic tool. Despite the small size of these RNA molecules, their impact on research within cell health is very large indeed.
Citations
Ahn, I., Kang, C. S., & Han, J. (2023). Where should siRNAs go: applicable organs for siRNA drugs. Experimental & Molecular Medicine, 55(7), 1283–1292. https://doi.org/10.1038/s12276-023-00998-y
Bong, A. H. L., Hua, T., So, C. L., Peters, A. A., Robitaille, M., Tan, Y. Y., Roberts-Thomson, S. J., & Monteith, G. R. (2022). AKT Regulation of ORAI1-Mediated Calcium Influx in Breast Cancer Cells. Cancers, 14(19). https://doi.org/10.3390/cancers14194794
Friedrich, M., & Aigner, A. (2022). Therapeutic siRNA: State-of-the-Art and Future Perspectives. In BioDrugs (Vol. 36, Issue 5, pp. 549–571). Adis. https://doi.org/10.1007/s40259-022-00549-3
Ha, M., Pang, M., Agarwal, V., & Chen, Z. J. (2008). Interspecies regulation of microRNAs and their targets. In Biochimica et Biophysica Acta – Gene Regulatory Mechanisms (Vol. 1779, Issue 11, pp. 735–742). https://doi.org/10.1016/j.bbagrm.2008.03.004
Wang, B., Zhang, J., & Xu, A. (2023). Recombinant Adenovirus siRNA Knocking Down the Ndufs4 Gene Alleviates Myocardial Apoptosis Induced by Oxidative Stress Injury. Cardiology Research and Practice, 2023. https://doi.org/10.1155/2023/8141129
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