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Identification of a LncRNA EPR—>METTL7A1 pathway modulating translation of select genes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE195823 | GEO | 2022/05/28

REPOSITORIES: GEO

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Identification of a LncRNA EPR—>METTL7A1 pathway modulating translation of select genes (Polysomes)

Project description:EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription and, here, we report on Mettl7a1 as a target of EPR. We show that the lncRNA induces Mettl7a1 transcription by remodeling the 3-dimensional chromatin structure at the Mettl7a1 locus. Our data indicate that METTL7A1 participates in the EPR-dependent pathway that antagonizes TGF-β signaling. METTL7A1 is absent in tumorigenic murine mammary gland cells and its human ortholog (METT7A) is downregulated in breast cancers. Importantly, expression of METTL7A1 in 4T1 tumorigenic cells reduces their transformation potential, and the putative methyltransferase activity of METTL7A1 appears dispensable for its biological functions. METTL7A1 is a cytoplasmic protein and, from a mechanistic perspective, interacts with factors implicated in the early steps of mRNA translation, associates with ribosomes, and affects the levels of select proteins without substantial changes in mRNA abundance. Our data suggest the possibility that METTL7A1 conveys the transcriptional regulation operated by EPR into specific changes of mRNA translation.

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Identification of a LncRNA EPR—>METTL7A1 pathway modulating translation of select genes (Total RNA)

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Identification of a LncRNA EPR—>METTL7A1 pathway modulating translation of select genes (3C-Seq)

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Identification of a LncRNA EPR—>METTL7A1 pathway modulating translation of select genes (Polysomes)

Project description:Identification of a LncRNA EPR—>METTL7A1 pathway modulating translation of select genes (Polysomes)

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Identification of a LncRNA EPR—>METTL7A1 pathway modulating translation of select genes (Total RNA)

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Identification of a LncRNA EPR—>METTL7A1 pathway modulating translation of select genes (3C-Seq)

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LncRNA EPR-induced METTL7A1 modulates target gene translation.

Project description:EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription. Here, we report on Mettl7a1 as a direct target of EPR. We show that EPR induces Mettl7a1 transcription by rewiring three-dimensional chromatin interactions at the Mettl7a1 locus. Our data indicate that METTL7A1 contributes to EPR-dependent inhibition of TGF-β signaling. METTL7A1 is absent in tumorigenic murine mammary gland cells and its human ortholog (METTL7A) is downregulated in breast cancers. Importantly, re-expression of METTL7A1 in 4T1 tumorigenic cells attenuates their transformation potential, with the putative methyltransferase activity of METTL7A1 being dispensable for its biological functions. We found that METTL7A1 localizes in the cytoplasm whereby it interacts with factors implicated in the early steps of mRNA translation, associates with ribosomes, and affects the levels of target proteins without altering mRNA abundance. Overall, our data indicates that METTL7A1-a transcriptional target of EPR-modulates translation of select transcripts.

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LncRNA EPR-induced METTL7A1 modulates target gene translation

Project description:EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription. Here, we report on Mettl7a1 as a direct target of EPR. We show that EPR induces Mettl7a1 transcription by rewiring three-dimensional chromatin interactions at the Mettl7a1 locus. Our data indicate that METTL7A1 contributes to EPR-dependent inhibition of TGF-β signaling. METTL7A1 is absent in tumorigenic murine mammary gland cells and its human ortholog (METTL7A) is downregulated in breast cancers. Importantly, re-expression of METTL7A1 in 4T1 tumorigenic cells attenuates their transformation potential, with the putative methyltransferase activity of METTL7A1 being dispensable for its biological functions. We found that METTL7A1 localizes in the cytoplasm whereby it interacts with factors implicated in the early steps of mRNA translation, associates with ribosomes, and affects the levels of target proteins without altering mRNA abundance. Overall, our data indicates that METTL7A1 —a transcriptional target of EPR— modulates translation of select transcripts.

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