Genes Protect Themselves Against Being Silenced

Harvard Stem Cell Institute (HSCI) researchers have settled a century-old debate over whether occurrence of DNA methylation acts to silence gene expression, or if genes are turned off by other means before they are methylated.

As explicated today in the journal Nature, methylation in fact enforces gene silencing, and it is levels of a newly identified form of RNA produced by individual genes that determines whether they are turned off by the addition of a methyl (CH3) group by the enzyme DNA methylase 1 (DNMT1).

The study, led by HSCI Principal Faculty member Daniel Tenen, MD, found that during transcription of DNA to RNA, a gene produces a small amount of what the investigators named “extracoding RNA,” which stays in the nucleus and binds to DNMT1, blocking its ability to methylate, or silence the gene. The discovery of RNA’s new function has therapeutic potential as an on-off switch for gene expression.

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