'Mysterious' non-protein-coding RNAs play important roles in gene expression

'Mysterious' non-protein-coding RNAs play important roles in gene expression

In cells, DNA is transcribed into RNAs that provide the molecular recipe for cells to make proteins. Most of the genome is transcribed into RNA, but only a small proportion of RNAs are actually from the protein-coding regions of the genome.

"Why are the non-coding regions transcribed at all? Their function has been mysterious," said the senior author.

Enhancers boost the rate of gene expression from nearby protein-coding genes so a cell can pump out more of a needed protein molecule. A mysterious subset of non-coding RNAs called enhancer RNAs (eRNAs) are transcribed from enhancer sequences. While these are important for boosting gene expression, how they achieve this has been completely unknown.

Shedding new light on these elusive eRNAs, authors showed that CBP, an enzyme that activates transcription from enhancers, binds directly to eRNAs. This simple act controls patterns of gene expression in organisms by regulating acetylation, a chemical mark that directs DNA tightly packed in the nucleus of cells to loosen to promote transcription. Their findings are published this week in Cell.

Using biochemical assays, authors showed that the region of CBP that binds to RNA also can regulate the ability of CBP to work with chemical mark. By binding to this region, eRNAs can directly stimulate CBPs' acetylation activity.

"There is increased interest in enhancers and eRNAs in the cancer biology world because defective enhancers can cause too much or too little of a protein to be made, or can cause the coding region to be turned off or on, or can make a protein at the wrong time," senior author said. Knowing more about how enhancers and eRNAs function will help oncologists, since recent DNA sequencing of tumors from humans show that numerous mutations associated with cancers and other diseases occur in enhancer regions of the genome -- not in protein-coding regions.