MicroRNA can serve as a "decoder ring" for understanding complex biological processes, a team of New York University chemists has found. Their study, which appears in Proceedings of the National Academy of Sciences, points to a new method for decrypting the biological functions of enzymes and identifying those that drive diseases.
The research focuses on a particular class of enzymes that biosynthesize carbohydrates (i.e. glycans)—complex biological molecules controlling multiple aspects of cell biology—as well as on their attendant microRNA (miRNA), which are regulatory molecules that spur changes in a cell by inhibiting protein expression.
"Carbohydrates present a challenge for analysis because their complexity and 'noise' that accompanies their biosynthesis make it difficult to isolate how they are involved in cellular change," explains Lara Mahal, an associate professor in NYU's Department of Chemistry and the study's senior author. "Our results show that rather than trying to trace the intricacies of this molecule's activity, we can simply track miRNA."
Specifically, she adds, miRNA can illuminate which glycogenes, or genes encoding glycosylation enzymes, are vital in a biological pathway.
Previous research by Mahal and her colleagues found that miRNA molecules—used to regulate gene expression—serve as major regulators of the cell's surface-level carbohydrates. The discovery showed, for the first time, that miRNA play a significant regulatory role in this part of the cell, also known as the glycome.
In the new study, her research team focused on determining whether miRNA could be used as a "decoder ring" to reveal the role of specific glycans in biology. They focused on miR-200, an miRNA family controlling the movement of cells in processes such as wound healing and tumor-cell metastasis, to determine if it could predict the biological function of a trio of glycans that are notoriously hard to monitor.
Their research found that disruption of these three glycans had the same effect as miR-200. For example, both miR-200 and cells in which any of these three glycans were disrupted lost their ability to move, a critical function in healing wounds and in cancer metastasis.
MiRNA are far easier to analyze than glycosylation and are a useful tool to shed light on the role of glycosylation in human diseases and afflictions. This is especially important as carbohydrates play important roles in every disease, which we have yet to understand, Mahal notes.
"Cleft palates, coronary artery disease, and other conditions involve biological pathways that we largely don't understand," she explains. "MiRNA, our findings suggest, may offer a way to cut through the clutter to better see, and comprehend, how these afflictions are manifested."
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miRNA proxy approach reveals hidden functions of glycosylation, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1502076112