Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784751821228605440 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9303270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT briatapaola lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT caputoluca lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT zapparoliettore lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT marcaccinielisa lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT passalacquamario lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT brondololorenzo lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT bordodomenico lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT rossiannalisa lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT nicolettichiara lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT buccigabriele lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT puripierlorenzo lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT ingaalberto lncrnaeprinducedmettl7a1modulatestargetgenetranslation AT gherziroberto lncrnaeprinducedmettl7a1modulatestargetgenetranslation |