A recent scientific study co-authored by an Estonian researcher Indrek Koppel showed how genomic DNA repeat sequences that were previously considered useless play an important role in repairing nerve damage.
The discovered mechanism may contribute to future treatment strategies for brain and spinal cord injury, as well as other nervous system disorders.
The peripheral nervous system includes the nerves that connect the brain and spinal cord to the rest of the body. Peripheral neurons can be extraordinarily large, with their extensions reaching up to about a meter’s length in adult humans. It has long puzzled neuroscientists and clinicians why damage to these nerves can heal, but central nervous system (comprising the brain and spinal cord) injuries are irreversible. Understanding the molecular mechanisms of these differences is one of the key questions in the field of neuronal repair.
In a new study published in Cell, researchers found that DNA repeat sequences known as SINEs (short interspersed nuclear elements) play a key role. According to Indrek Koppel, Assistant Professor at the Department of Chemistry and Biotechnology at Tallinn University of Technology, SINE elements make up more than ten percent of the human genome and have been regarded as the most useless parts of our DNA.
“These high-copy-number sequences are like genomic parasites. They sometimes like to replicate themselves, but as far as we know, they have been shown to do very little that is beneficial to the host,” he said. “Now we know that following an injury to the peripheral nervous system, neurons begin actively producing non-protein coding RNA from these SINE repeat sequences,” said Koppel.
Experiments showed that the function supporting nerve cell regeneration can also be switched off. When the research team inhibited RNA production, the regrowth of nerve fibres slowed down. The team next explored whether this mechanism might also be at work in the central nervous system. This capability is particularly important, as the central nervous system recovers significantly less effectively than the peripheral nervous system. Researchers were able to artificially activate the same RNA production mechanism in the central nervous system, showing that the brain and spinal cord can be stimulated to repair themselves.
“Finding a function important for the nervous system in what had been considered a pile of genomic junk was new and unexpected. Hopefully, this new perspective on the molecular mechanisms of nerve injury can be used in the development of innovative treatments for spinal cord or brain injuries, or even neurodegenerative diseases such as Alzheimer’s disease or ALS” said Indrek Koppel.
The study was carried out in collaboration with several research groups and led by the molecular neurobiology team of Professor Mike Fainzilber at the Weizmann Institute of Science in Israel, and co-first authored by Dr Eitan Erez Zahavi (Weizmann Institute of Science) and Dr Indrek Koppel.
Reference: Repeat-element RNAs integrate a neuronal growth circuit. Zahavi, Eitan Erez et al. Cell, Volume 188, Issue 16, 4350 - 4365.e22