Putative Role for METTL1 in Human Gliobastoma
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Glioblastoma multiforme (GBM) is a deadly cancer affecting the late adult and elderly population. Although GBM can be subdivided into a number of distinct types, aberrant methylation effects define certain subtypes, such as the glioblastoma CpG island methylator phenotype (G-CIMP) subtype, and more recently, the proneural subtype. In GBM as a whole, gene amplification of methyltransferases – enzymes that catalyze the transfer of a -CH3 methyl group to nucleic acids - are a common theme. This type of gene amplification event leads to hyper-activity of the enzyme, and contributes to the methylator phenotype; however, the role that the methylator phenotype plays in GBM not completely understood. Here we mined cancer genome datasets for alterations of methyltransferases that target the nucleic acid, transfer RNA (tRNA). METTL1 was identified as the highest amplified tRNA methyltransferase in glioblastomas. METTL1's orthologue in yeast, TRM8, has been studied to some extent, and is known to target several tRNA species (tRNAVAL-AAC, tRNAMET, tRNAPHE, tRNAVAL) as part of the cell’s response to heat shock (REF). Overall, this work suggests a putative role for tRNA methylation in GBM formation through the amplification of METTL1, and suggests that tRNA methylation is an important component of the methylator phenotype. Future work will be to identify which tRNAs are targeted by METTL1 and the role it plays in the development of GBM.
Poster Presented at the 2017 SUNY Polytechnic Institute Student Project Showcase