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MiR-34a directly targets tRNAiMet precursors and affects cellular proliferation, cell cycle, and apoptosis.

ABSTRACT: It remains unknown whether microRNA (miRNA/miR) can target transfer RNA (tRNA) molecules. Here we provide evidence that miR-34a physically interacts with and functionally targets tRNAiMet precursors in both in vitro pulldown and Argonaute 2 (AGO2) cleavage assays. We find that miR-34a suppresses breast carcinogenesis, at least in part by lowering the levels of tRNAiMet through AGO2-mediated repression, consequently inhibiting the proliferation of breast cancer cells and inducing cell cycle arrest and apoptosis. Moreover, miR-34a expression is negatively correlated with tRNAiMet levels in cancer cell lines. Furthermore, we find that tRNAiMet knockdown also reduces cell proliferation while inducing cell cycle arrest and apoptosis. Conversely, ectopic expression of tRNAiMet promotes cell proliferation, inhibits apoptosis, and accelerates the S/G2 transition. Moreover, the enforced expression of modified tRNAiMet completely restores the phenotypic changes induced by miR-34a. Our results demonstrate that miR-34a directly targets tRNAiMet precursors via AGO2-mediated cleavage, and that tRNAiMet functions as an oncogene, potentially representing a target molecule for therapeutic intervention.

SUBMITTER: Wang B

PROVIDER: S-EPMC6048500 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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miR-34a directly targets tRNAiMet precursors and affects cellular proliferation, cell cycle, and apoptosis.

Wang Bo B Li Dongping D Kovalchuk Igor I Apel Ingrid J IJ Chinnaiyan Arul M AM Wóycicki Rafał K RK Cantor Charles R CR Kovalchuk Olga O

Proceedings of the National Academy of Sciences of the United States of America 20180625 28

It remains unknown whether microRNA (miRNA/miR) can target transfer RNA (tRNA) molecules. Here we provide evidence that miR-34a physically interacts with and functionally targets tRNAiMet precursors in both in vitro pulldown and Argonaute 2 (AGO2) cleavage assays. We find that miR-34a suppresses breast carcinogenesis, at least in part by lowering the levels of tRNAiMet through AGO2-mediated repression, consequently inhibiting the proliferation of breas ...[more]

PMID: 29941603

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MiR-34a directly targets tRNAiMet precursors and affects cellular proliferation, cell cycle, and apoptosis.

Publications

miR-34a directly targets tRNA<sub>i</sub><sup>Met</sup> precursors and affects cellular proliferation, cell cycle, and apoptosis.

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