LncRNA EPR-induced METTL7A1 modulates target gene translation

Abstract

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.

Epigenetic Regulation of CYP72A385-Mediated Metabolic Resistance to Novel Auxin Herbicide Florpyrauxifen-benzyl in Echinochloa crus-galli (L.) P. Beauv

“…This indicates that Region-3 interacted less with EcMETTL7A than Region-1 and Region-2. To further verify that EcMETTL7A specifically binds to the EcCYP72A385 promoter, we mutated the active site of EcMETTL7A (Figure S5f) and the aspartic acid (D) at position 146 to asparagine (N) . Both in vivo and in vitro, the EcMETTL7A D‑146‑N protein was significantly less attractive to the EcCYP72A385 promoter than the nonmutated protein (Figure S5).…”

“…METTL7A has been identified as an RNA methyltransferase that methylates DNA and long noncoding RNA to modulate target gene translation, and its lower expression has been found in different cancer cells. ,, For example, METTL7A1 is absent in tumorigenic murine mammary gland cells, its human ortholog ( METTL7A ) is downregulated in breast cancers, and re-expression of METTL7A1 in 4T1 tumorigenic cells attenuates their transformation potential . In contrast, METTL7A plays a role in the translational regulation of cell biological processes.…”

“…29,54,55 For example, METTL7A1 is absent in tumorigenic murine mammary gland cells, its human ortholog (METTL7A) is downregulated in breast cancers, and re-expression of METTL7A1 in 4T1 tumorigenic cells attenuates their transformation potential. 39 In contrast, METTL7A plays a role in the translational regulation of cell biological processes. Some studies have reported that METTL7A can activate immune-related pathways and the P53 signaling pathway to inhibit melanoma progression.…”

“…To further verify that EcMETTL7A specifically binds to the EcCYP72A385 promoter, we mutated the active site of EcMETTL7A (Figure S5f) and the aspartic acid (D) at position 146 to asparagine (N). 39 Both in vivo and in vitro, the EcMETTL7A D-146-N protein was significantly less attractive to the EcCYP72A385 promoter than the nonmutated protein (Figure S5). In contrast, EcROS1.1 did not exhibit the ability to bind to the promoter of EcCYP72A385 (Figure S5g).…”