miRNA Proxy Hypothesis
miRNAs, or miRs, are short non-coding RNA strands that bind to mRNAs to regulate gene expression. Our miRNA proxy hypothesis states that:
“if a miR drives a specific biological phenotype, the targets of that miR will drive the same biological phenotype. Thus, miRs can be used to identify (by proxy) the biological functions of specific glycosylation enzymes (or other proteins).”
With this, we may be able to identify crucial glycosylation enzymes driving disease states. Additionally, our research provides novel insight into the precise control miRs have over protein expression – that is, miRs also have the capability of activating gene expression.
Fluorescent ratiometric assay to identify miR:3′-UTR interactions (miRFluR)
- Agrawal, P.; Kurcon, T.; Pilobello, K.T.; Rakus, J.F.; Koppolu, S.; Liu, Z.; Batista, B.S.; Eng, W.S., Hsu, K.-L.; Liang, Y.; Mahal, L.K. Mapping post-transcriptional regulation of the human glycome uncovers microRNA defining the glycocode. Proc. Natl. Acad. Sci., USA, 2014, 111, 4338-43. doi: 10.1073/pnas.1321524111
- Kasper, B.T.; Koppolu, S.; Mahal, L.K. Insights into miRNA regulation of the human glycome. Biochem. Biophys. Res. Commun., 2014, 445, 774-9. doi: 10.1016/j.bbrc.2014.01.034
- Kurcon, T.; Liu, Z.; Paradkar, A.V.; Vaiana, C.A.; Koppolu, S.; Agrawal, P.; Mahal, L.K. miRNA proxy approach reveals hidden functions of glycosylation. Proc. Natl. Acad. Sci., USA, 2015, 112, 7327-32. doi: 10.1073/pnas.1502076112
- Vaiana, C.A.; Kurcon, T.; Mahal, L.K. MicroRNA-424 predicts a role for β-1,4 branched glycosylation in cell cycle progression. J. Biol. Chem., 2016, 291, 1529-37. doi: 10.1074/jbc.M115.672220
- Thu, T.C.; Chung, J.Y.; Dhawan, D.; Vaiana, C.A.; Mahal, L.K. High-throughput miRFluR platform identifies miRNA regulating B3GLCT that predict Peters’ Plus Syndrome phenotype, supporting the miRNA proxy hypothesis. ACS Chemical Biology, 2021, 16, 1900-1907. doi: 10.1021/acschembio.1c00247. Formerly bioRixv doi: 10.1101/2021.04.01.43813
- Jame-Chenarboo, F.; Ng, H.H.; Macdonald, D.; Mahal, L.K. High-throughput analysis reveals miRNA upregulating α-2,6-sialic acid through direct miRNA–mRNA interactions. ACS Central Science, 2022, in Press. doi: 10.1021/acscentsci.2c00748. Formerly bioRixv doi: 10.1101/2022.04.01.486772
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The Canada Excellence Research Chairs (CERC) Program awards universities up to $10 million over seven years to support world‑renowned researchers and their teams to establish ambitious research programs at Canadian universities.
Located in beautiful Edmonton, Alberta, Canada, the Chemistry Department at the UofA is renown for its active research. It is one of the best equipped and well funded departments in Canada.
It is a glycomic technology developed in the Mahal Lab, provide a rapid analysis of the glycome (1-3). These microarrays utilize immobilized carbohydrate-binding proteins at high spatial density to give specific information on the repertoire of glycans present.
miRNA can be used to identify glycosylation enzymes and their corresponding glycans that drive disease states.
At the UofA, you do not have to find a supervisor in order to apply. The department has a process in place for students to find a supervisor and join a research group once they arrive to start their program. However, it is recommended for applicants to contact chemistry faculty members whose areas of research are of interest to you. Information about requirements and how to apply can be found here.