Abstract

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 are observed in many diseases. Therefore, understanding the mechanisms behind alteration of DNMT1 activity is important. Here, we show that CCDC26, a nuclear long non-coding RNA frequently mutated in myeloid leukaemia, directly interacts with DNMT1. In the absence of CCDC26 RNA, DNMT1 is mis-located in the cytoplasm. As a result, genomic DNA is significantly hypomethylated, which is accompanied by a slower cell growth rate and increased cell death. These results point to a previously unrecognised mechanism of long non-coding RNA mediated subcellular localisation of DNMT1 and regulation of DNA methylation. These observations are significant given the importance of DNMT1 in cancer and number of other diseases.