Noncoding RNA Helps Cells Recover from DNA Damage

Scientists discover transcripts from the same gene that can express both proteins and noncoding RNA.  

May 1, 2017
Diana Kwon

TWO-FACED: mRNA (left, red) from the ASCC3 gene is mostly in the cytoplasm, while ASCC3’s noncoding RNA (right, red) is in the cell nucleus (blue). LAURA WILLIAMSON AND BRADLEY SPENCER-DENE

The paper
L. Williamson et al., “UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene,” Cell, doi:10.1016/j.cell.2017.01.019, 2017.

Damaged DNA
When its DNA is damaged, a cell activates genes to repair the lesion and slows down the transcription of many others. According to Jesper Svejstrup of the Francis Crick Institute, researchers have known about this response for a few decades. However, “that was the extent of what we knew,” he says.

Two for one
Last year, Svejstrup and colleagues identified factors associated with transcription-related changes after UV-induced DNA damage, including the transcription of ASCC3, which encodes a protein involved in regulating gene expression (Cell Rep, 15:1597-1610, 2016). In their latest study using sequencing analysis, they discovered that normally long ASCC3 transcripts became much shorter after damage.

Functional see-saws
Knocking down the short ASCC3 transcript produced after UV exposure prevented the cell from recovering normal levels of transcription. “Without the short isoform of ASCC3, you can no longer respond correctly to DNA damage, and cells die,” Svejstrup explains. Blocking the long version, on the other hand, increased transcription levels after UV irradiation. “It’s interesting because the same gene, ASCC3, is producing two opposed [functions],” says Alberto Kornblihtt, a molecular biologist at the University of Buenos Aires who was not involved in the work. “If the protein is made from the long pre-mRNA, then global transcription is repressed. But if the short RNA is made, it helps recover transcription hours after damage.”

Uncovering mechanisms
How the short isoform aids repair remains unknown. “The most logical, simple explanation is that the [noncoding RNA] counteracts the protein encoding form,” Svejstrup says. “Perhaps [it] binds to ASCC3 protein—but we haven’t been able to get clear evidence for that [yet].”

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