MO18-6 The tumor suppression potential of RNA pseudouridine synthase family via microRNA regulation

Abstract

MicroRNAs are non-coding RNAs consisting of about 22 nucleotides that regulate a large number of mRNAs. Among them, let-7 is one of the first microRNAs to be identified and has tumor suppressive potential through regulation of KRAS and MYC mRNAs. We have shown that TruB1, one of the tRNA pseudouridine synthetases, regulates let-7 relatively specifically by cell-based screening (Kurimoto et al. EMBO J. 2020). In the present study, to evaluate the specificity of the let-7-mediated tumor suppressor ability of TruB1, we examined the effects of whole RNA pseudouridine synthetase on the regulation of its let-7 in vitro experiments and in the reported literatures. The results showed that DKC1 and PUS10 also regulate microRNAs of different sub-subset from let-7 in the reported literatures, whereas TruB2 may regulate microRNA subset including let-7. We will discuss about clinical impact of TruB2 on several cancers by TCGA database. These new functions of RNA-pseudouridine enzymes might have the impact on the tumor-suppressive potential. These results are significant from a molecular biological point of view, leading to a clarification of the regulatory mechanism.