# Small RNA-mediated DNA (cytosine-5) methyltransferase 1 inhibition leads to aberrant DNA methylation

## TL;DR

This paper shows that certain small RNAs can inhibit a key DNA methylation enzyme, leading to abnormal DNA methylation patterns and gene activation.

## Contribution

The study reveals a novel mechanism where miRNAs directly inhibit DNMT1, causing genome-wide methylation changes.

## Key findings

- miR-155-5p binds to DNMT1 and inhibits its activity.
- Exogenous miR-155-5p causes genome hypomethylation and gene activation.
- Aberrant DNA methylation patterns include both hypomethylation and small hypermethylation shifts.

## Abstract

Mammalian cells contain copious amounts of RNA including both coding and noncoding RNA (ncRNA). Generally the ncRNAs function to regulate gene expression at the transcriptional and post-transcriptional level. Among ncRNA, the long ncRNA and small ncRNA can affect histone modification, DNA methylation targeting and gene silencing. Here we show that endogenous DNA methyltransferase 1 (DNMT1) co-purifies with inhibitory ncRNAs. MicroRNAs (miRNAs) bind directly to DNMT1 with high affinity. The binding of miRNAs, such as miR-155-5p, leads to inhibition of DNMT1 enzyme activity. Exogenous miR-155-5p in cells induces aberrant DNA methylation of the genome, resulting in hypomethylation of low to moderately methylated regions. And small shift of hypermethylation of previously hypomethylated region was also observed. Furthermore, hypomethylation led to activation of genes. Based on these observations, overexpression of miR-155-5p resulted in aberrant DNA methylation by inhibiting DNMT1 activity, resulting in altered gene expression.