A new role for RNA in safeguarding human chromosome number

A new role for RNA in safeguarding human chromosome number

Molecular biologists at UT Southwestern Medical Center have identified a gene called NORAD that helps maintain the proper number of chromosomes in cells, and that when inactivated, causes the number of chromosomes in a cell to become unstable, a key feature of cancer cells.

The NORAD gene, however, does not encode a protein. Instead, NORAD produces a long noncoding RNA, a type of molecule that was not previously known to be important in chromosome maintenance, the researchers report in the journal Cell.

Researchers began studying this particular molecule because the RNA kicks into action after DNA is damaged; they therefore termed it Noncoding RNA Activated by DNA Damage, or NORAD.

The scientists unexpectedly found that NORAD plays a critical role in keeping the genome stable, and conducted experiments showing that when NORAD is absent, cells frequently lose or gain whole chromosomes.

Microscopic imaging revealed that cells lacking NORAD are unable to properly pass on chromosomes as they divide. NORAD controls chromosome segregation during cell division by regulating the activity of a family of proteins called PUMILIO proteins.

In cells lacking NORAD, overactivity of PUMILIO leads to an unstable genome. Since most cancer cells also exhibit genomic instability, researchers are now exploring whether abnormal function of NORAD or PUMILIO proteins contribute to human tumors.