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LncRNA EPR-induced METTL7A1 modulates target gene translation
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2022-06-24 , DOI: 10.1093/nar/gkac544
Paola Briata 1 , Luca Caputo 2 , Ettore Zapparoli 3 , Elisa Marcaccini 1 , Mario Passalacqua 4, 5 , Lorenzo Brondolo 1 , Domenico Bordo 1 , Annalisa Rossi 6 , Chiara Nicoletti 2 , Gabriele Bucci 3 , Pier Lorenzo Puri 2 , Alberto Inga 6 , Roberto Gherzi 1
Affiliation  

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.

中文翻译:

LncRNA EPR 诱导的 METTL7A1 调节靶基因翻译

EPR 是一种长链非编码 RNA (lncRNA),通过调节基因转录来控制乳腺细胞的细胞增殖。在这里,我们将 Mettl7a1 报告为 EPR 的直接目标。我们表明 EPR 通过重新连接 Mettl7a1 基因座处的三维染色质相互作用来诱导 Mettl7a1 转录。我们的数据表明 METTL7A1 有助于 TGF-β 信号转导的 EPR 依赖性抑制。METTL7A1 在致瘤性小鼠乳腺细胞中不存在,其人类直系同源物 (METTL7A) 在乳腺癌中下调。重要的是,METTL7A1 在 4T1 致瘤细胞中的重新表达减弱了它们的转化潜力,METTL7A1 的推定甲基转移酶活性对其生物学功能而言是可有可无的。我们发现 METTL7A1 定位于细胞质中,从而与 mRNA 翻译早期步骤中涉及的因素相互作用,与核糖体结合,并在不改变 mRNA 丰度的情况下影响靶蛋白的水平。总体而言,我们的数据表明 METTL7A1(EPR 的转录靶标)调节选定转录本的翻译。
更新日期:2022-06-24
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