A long intergenic non-coding RNA regulates nuclear localization of DNA methyl transferase-1

Jones, Rhian, Wijesinghe, Susanne, Wilson, Claire ORCID: 0000-0003-0456-1350, Halsall, John, Liloglou, Triantafillos ORCID: 0000-0003-0460-1404 and Kanhere, Aditi
(2021) A long intergenic non-coding RNA regulates nuclear localization of DNA methyl transferase-1. ISCIENCE, 24 (4). 102273-.

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DNA methyl transferase-1 or DNMT1 maintains DNA methylation in the genome and is important for regulating gene expression in cells. Aberrant changes in DNMT1 activity and DNA methylation are commonly observed in cancers and many other diseases. Recently, a number of long intergenic non-protein-coding RNAs or lincRNAs have been shown to play a role in regulating DNMT1 activity. <i>CCDC26</i> is a nuclear lincRNA that is frequently mutated in cancers and is a hotbed for disease-associated single nucleotide changes. However, the functional mechanism of <i>CCDC26</i> is not understood. Here, we show that this lincRNA is concentrated on the nuclear periphery. Strikingly, in the absence of <i>CCDC26</i> lincRNA, DNMT1 is mis-located in the cytoplasm, and the genomic DNA is significantly hypomethylated. This is accompanied by double-stranded DNA breaks and increased cell death. These results point to a previously unrecognized mechanism of lincRNA-mediated subcellular localization of DNMT1 and regulation of DNA methylation.

Item Type: Article
Uncontrolled Keywords: Cell Biology, Molecular Biology
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 07 Jul 2021 10:07
Last Modified: 18 Jan 2023 21:36
DOI: 10.1016/j.isci.2021.102273
Open Access URL: https://doi.org/10.1016/j.isci.2021.102273
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3129116