microRNA molecules upregulate proteins instead of dampening it

microRNAs are thought to only suppress protein expression in dividing cells, such as tumor cells, and can contribute to the development of cancer. Conventional wisdom is contradicted by new research, which was published in ACS Central Science, which demonstrates that some of these tiny molecules can increase the expression of a particular gene in dividing human cells and in cancer cells.

microRNA molecules upregulate proteins instead of dampening it
microRNA molecules, as shown in this illustration, can upregulate proteins in addition to downregulating them. Image Credit: nobeastsofierce/Shutterstock.com

microRNAs, also known as miRNAs, are very short RNA molecules that do not code for proteins. Instead, they largely suppress, or downregulate, protein synthesis by preventing the expression of particular genes.

The enzymes in charge of mediating the glycosylation process, which involves the addition of carbohydrates to specific proteins, are one class of cellular machinery that miRNAs control.

However, this process can be severely dysregulated in cancer cells, which raises the possibility that miRNAs are acting in an unusual way. Therefore, Lara Mahal and colleagues set out to examine the precise role that miRNAs play during the glycosylation process and determine whether the molecules could be acting in a novel manner.

Prior to this, the scientists created a fluorescence assay that can assess how miRNAs interact with their targets and whether they boost or suppress protein synthesis. With the aid of the assay, they looked into how the cancer-related glycosylation enzymes ST6GAL1 and ST6GAL2 were regulated.

They discovered that for the former, the miRNAs appeared to directly upregulate the process in human cells that were not cancerous. This calls into question the conventional wisdom that miRNAs only suppress protein synthesis.

The same results were seen when they examined multiple cancer cell lines for miRNA-mediated upregulation. According to the researchers, this work advances the understanding of how miRNAs function, which is crucial when using miRNA-based therapeutics in both ongoing and upcoming clinical trials.

Journal reference:

Jame-Chenarboo, F., et al. (2022). High-Throughput Analysis Reveals miRNA Upregulating α-2,6-Sialic Acid through Direct miRNA–mRNA Interactions. ACS Central Science. doi.org/10.1021/acscentsci.2c00748


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