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LncRNA EPR-induced METTL7A1 modulates target gene translation

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...

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Autores principales: Briata, Paola, Caputo, Luca, Zapparoli, Ettore, Marcaccini, Elisa, Passalacqua, Mario, Brondolo, Lorenzo, Bordo, Domenico, Rossi, Annalisa, Nicoletti, Chiara, Bucci, Gabriele, Puri, Pier Lorenzo, Inga, Alberto, Gherzi, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303270/
https://www.ncbi.nlm.nih.gov/pubmed/35748870
http://dx.doi.org/10.1093/nar/gkac544
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author Briata, Paola
Caputo, Luca
Zapparoli, Ettore
Marcaccini, Elisa
Passalacqua, Mario
Brondolo, Lorenzo
Bordo, Domenico
Rossi, Annalisa
Nicoletti, Chiara
Bucci, Gabriele
Puri, Pier Lorenzo
Inga, Alberto
Gherzi, Roberto
author_facet Briata, Paola
Caputo, Luca
Zapparoli, Ettore
Marcaccini, Elisa
Passalacqua, Mario
Brondolo, Lorenzo
Bordo, Domenico
Rossi, Annalisa
Nicoletti, Chiara
Bucci, Gabriele
Puri, Pier Lorenzo
Inga, Alberto
Gherzi, Roberto
author_sort Briata, Paola
collection PubMed
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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spelling pubmed-93032702022-07-22 LncRNA EPR-induced METTL7A1 modulates target gene translation Briata, Paola Caputo, Luca Zapparoli, Ettore Marcaccini, Elisa Passalacqua, Mario Brondolo, Lorenzo Bordo, Domenico Rossi, Annalisa Nicoletti, Chiara Bucci, Gabriele Puri, Pier Lorenzo Inga, Alberto Gherzi, Roberto Nucleic Acids Res RNA and RNA-protein complexes 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. Oxford University Press 2022-06-24 /pmc/articles/PMC9303270/ /pubmed/35748870 http://dx.doi.org/10.1093/nar/gkac544 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA and RNA-protein complexes
Briata, Paola
Caputo, Luca
Zapparoli, Ettore
Marcaccini, Elisa
Passalacqua, Mario
Brondolo, Lorenzo
Bordo, Domenico
Rossi, Annalisa
Nicoletti, Chiara
Bucci, Gabriele
Puri, Pier Lorenzo
Inga, Alberto
Gherzi, Roberto
LncRNA EPR-induced METTL7A1 modulates target gene translation
title LncRNA EPR-induced METTL7A1 modulates target gene translation
title_full LncRNA EPR-induced METTL7A1 modulates target gene translation
title_fullStr LncRNA EPR-induced METTL7A1 modulates target gene translation
title_full_unstemmed LncRNA EPR-induced METTL7A1 modulates target gene translation
title_short LncRNA EPR-induced METTL7A1 modulates target gene translation
title_sort lncrna epr-induced mettl7a1 modulates target gene translation
topic RNA and RNA-protein complexes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303270/
https://www.ncbi.nlm.nih.gov/pubmed/35748870
http://dx.doi.org/10.1093/nar/gkac544
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