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Charged tRNA profiling of mcf10a, HCC1806 cells, polysome profiling, RNA-Seq and Ribo-Seq in 4T07 cells upon LARS knockdown by shRNA, and RNA-Seq of ribosome-associated RNAs in Lars depleted PyMT tumors

ABSTRACT: In this study, we identify leucyl-tRNA synthetase (LARS) as a breast tumor suppressor. To identify the mechanism underlying LARS-mediated breast tumor suppression, we first conducted charged tRNA profiling to assess charged and total tRNA-Leu expression in cell lines with high and low LARS expression. Expression of select charged and total tRNA-Leu isoacceptors were reduced in cell lines with lower LARS expression. We then conducted RNA-Seq and translation profiling including ribosome profiling (Ribo-Seq), polysome profiling in LARS-depleted cell lines. To test our hypothesis in vivo, we also performed RNA-Seq of ribosome-associated RNAs in Lars depleted PyMT tumors within RiboTag mice. The analyses implicate LARS as a regulator of leucine-rich translation.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE176130 | GEO | 2022/01/05

REPOSITORIES: GEO

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Charged tRNA profiling of mcf10a, HCC1806 cells, polysome profiling, RNA-Seq and Ribo-Seq in 4T07 cells upon LARS knockdown by shRNA, and RNA-Seq of ribosome-associated RNAs in Lars depleted PyMT tumors

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Project description:In this study, we identify leucyl-tRNA synthetase (LARS) as a breast tumor suppressor. To identify the mechanism underlying LARS-mediated breast tumor suppression, we conducted TMT-proteomics in PyMT mouse tumors with monoallelic genetic deletion of LARS in the mammary tumor compartment. The analyses implicate LARS as a regulator of leucine-rich protein translation resulting in downregulation of candidate leucine-rich tumor suppressor genes.

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