Folate regulates RNA m5C modification and translation in neural stem cells

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dc.contributor.authorXu, Xiguangen
dc.contributor.authorJohnson, Zacharyen
dc.contributor.authorWang, Amandaen
dc.contributor.authorPadget, Rachel L.en
dc.contributor.authorSmyth, James W.en
dc.contributor.authorXie, Hehuangen
dc.date.accessioned2022-11-28T13:46:23Zen
dc.date.available2022-11-28T13:46:23Zen
dc.date.issued2022-11-23en
dc.date.updated2022-11-27T04:12:10Zen
dc.description.abstractBackground Folate is an essential B-group vitamin and a key methyl donor with important biological functions including DNA methylation regulation. Normal neurodevelopment and physiology are sensitive to the cellular folate levels. Either deficiency or excess of folate may lead to neurological disorders. Recently, folate has been linked to tRNA cytosine-5 methylation (m5C) and translation in mammalian mitochondria. However, the influence of folate intake on neuronal mRNA m5C modification and translation remains largely unknown. Here, we provide transcriptome-wide landscapes of m5C modification in poly(A)-enriched RNAs together with mRNA transcription and translation profiles for mouse neural stem cells (NSCs) cultured in three different concentrations of folate. Results NSCs cultured in three different concentrations of folate showed distinct mRNA methylation profiles. Despite uncovering only a few differentially expressed genes, hundreds of differentially translated genes were identified in NSCs with folate deficiency or supplementation. The differentially translated genes induced by low folate are associated with cytoplasmic translation and mitochondrial function, while the differentially translated genes induced by high folate are associated with increased neural stem cell proliferation. Interestingly, compared to total mRNAs, polysome mRNAs contained high levels of m5C. Furthermore, an integrative analysis indicated a transcript-specific relationship between RNA m5C methylation and mRNA translation efficiency. Conclusions Altogether, our study reports a transcriptome-wide influence of folate on mRNA m5C methylation and translation in NSCs and reveals a potential link between mRNA m5C methylation and mRNA translation.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBMC Biology. 2022 Nov 23;20(1):261en
dc.identifier.doihttps://doi.org/10.1186/s12915-022-01467-0en
dc.identifier.urihttp://hdl.handle.net/10919/112703en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderThe Author(s)en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleFolate regulates RNA m5C modification and translation in neural stem cellsen
dc.title.serialBMC Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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